Index: Evolution's Clinical Guidebook

In the past few blogs, I've been discussing the recent publication of my book, Evolution’s Clinical Guidebook: Translating Ancient Genes Into Precision Medicine. The premise of this book is that modern medicine is based on an understanding of evolutionary processes. Evolution shows us the relationships between the subdisciplines of medicine that benefit directly from Precision Medicine (i.e., pathology, microbiology, clinical genetics, pharmacology, and bioinformatics). In Evolution's Clinical Guidebook, all of these diverse fields are brought together, under the subject of evolution. To illustrate, I have listed below the first few pages of the index to the book (letters A through H). Just by perusing these index terms, you can get some idea of the role played by evolution as the great unifier of modern medicine.

Partial Book Index

A 
Abiogenesis 
  catalysts, 2 
  cellular life, 
  earliest signs of, 4 
  definition, 1
  DNA, 4 
  evolution, 2 
  life on earth, 1 
  natural selection, 2
  RNA, 4­5
Acanthodians, 215
Acarnus erithacus, 192, 192f 
Acidianus Tailed Virus, 160
Acquired disease, 20, 29-­30
Actin, 17
Actinistia, 216
Actinopterygii, 215
Adaptive immune system, 214
Adaptive immunity, 161, 164
Adenocarcinoma, 125, 126-­127f Adult organisms, 94, 102
Agenesis of the Corpus Callosum (ACC), 222
Aging, 77, 216, 257-­258, 261-­265 
  vs. diseases of old people, 257-­259 
  evolution of, 252­-265 gene, 257­-258
Agnatha, 214
Allele, 77
Allium cepa, 66
Allium ursinum, 66 alphaA-Crystallin, 18
Alstrom syndrome, 213-­214
Alternative RNA splicing, 126
Amanita phalloides, 155
Amborella trichopoda, 150
Ambulacraria, 197
Amniotes, 218
Amoebozoa, 184, 290
Amphibia, 216­218
Amphioxus, 150
Amyloid world, 30
Anatomy, 246
Ancestral classes, 175-­176, 196­-197
Ancestral lineage, 12
Ancestral species, 12
  eukaryotic development, steps in, 14-­15, 15f 
  gene families, 13­-14
Ancylostoma duodenale, 292
Androgenesis, 221
Aneuploidy, 69­70, 70f Angelman syndrome, 222
Angiogenesis, 126
Angiosperma, 29­-44
Animal cells, 262
Animalia, 27f 
Animal model, human disease 
  Koch's postulates and reliance, 299-­300 
  nonhuman eutherians, 285 
  non-vertebrate models, cancer research, 298-­299 
  for orthodiseases
    Caenorhabditis elegans (nematodes), 294, 296-­298, 297f
    Danio rerio (zebrafish), 294, 297-­298, 298f 
    Drosophila melanogaster (fruit fly), 294, 297 
  homologous genes, 296 
  human pathologic processes, 295 
  orthologous genes, 295­-296
  Saccharomyces cerevisiae (yeast), 294­-296, 296f 
  rabbits, myxoma virus on, 300-­302 
  rats, 285 
  specificities and idiosyncrasies
    clinical trial, 286­-287
    Gram-negative organisms, 286 
    infections, history of, 290­-291, 293-­294 
    inflammatory response, 287 
    lipopolysaccharide, 286 
    mice, 286­288 
    microorganisms, potential pathogens, 288-­290 
    rodent models, 287-­288
  TGN1412, 286­287
Anlagen, 127
Aplastic anemia, 270
Apoikozoa, 186­-187
Apomorphy, 198
Apoptosis, 53
Archaea, 26, 27f 
Archaeplastida, 14-­15, 28, 186
Archiplastidae, 185
Arrhythmogenic cardiomyopathies, 191
Arthropods, hepatopancreas of, 118-­119
Ascaris lumbricoides, 292
Aspergillus flavus, 155
Association vs. cause, 77
Ataxia telangiectasia, 30
Atlantogenata, 229
Autism, 58
Autoantibody disease vs. autoimmune disease, 233
Autosomal dominance, 270
Azacytidine, 122

B 
Bacillus globigii, 288
Bacillus subtilis, 244
Bacteria, 26
Baraitser-Winter syndrome, 57
Bartonella species, 26
Basal cell carcinomas, 223-­224, 223f Basal layer, 255
Benign tumor, 218, 233
Bikonta, 183­184
Bilateria, 94, 193­203, 254
Bioinformatics, 78
Biological diversity, 152
Biological theory, 308
Biopsy specimen, 255f Biosphere, 157
Biosynthetic cycle, 17
BK polyomavirus, 292
Blastocystis hominis, 289
Blastula, 191
Blastulation, 189, 190f Blended class, 322, 325
Blood, photomicrograph of, 108f Bloom syndrome, 262
Bone marrow, 256
Bookie, 266
Bootstrapping paradoxes, 5
  chicken and egg paradox, 6­8 
  enzyme and enzyme-synthesizing machinery, 8 
  general solution for, 11-­12 
  hardware or software, 5­6 
  process of evolution and product of evolution, 9-­10
  RNA and DNA, 8­9, 10f 
  species and class of animals, 10-­11
Borderland of Embryology and Pathology, 118-­120
Boreoeutheria, 229
Borhing-Opitz syndrome, 57
Brassica oleracea, 158
BRCA, 271
BRCA1 gene, 269
BRCA2 gene, 269
Breast cancer, 260
Breeds, 248, 249f Brugia malayi, 292
Bryophyte life cycle, 7
Bryophytes, 7
BUB1B gene, 70
Bubonic plague, 292
Bungarus caeruleus, 110f "But-for" test, 30

C 
Caenorhabditis elegans, 65, 123, 294, 296-­298, 297f Calvin cycle, 17
Cambrian explosion, 21­-25, 21­-22f, 155-­156, 185 
  coexistence and coevolution, 25­26
  animals (class Metazoa), 28
  Archaea, 26, 27f 
  Archaeplastida (plants), 28 
  bacteria, 26 
  fungi, 28 
  single-celled eukaryotes, 28 
  viruses, 26
Cambrian period, 21-­22, 22f, 24
Cancer, 259­261
Cancer cells, 51
Cancer progression, 30
Carcinogen, 127
Carcinogenesis, 17, 30-­31, 223
Carcinoid tumors, 211
Carcinosarcomas, of uterus, 119
Caretaker diploid organism, 7
Carotenoids, 156
Carrier, 26, 31 asymptomatic, 27
Catarrhini, 231
Cause, 19, 24, 28
Cell types, epigenome and evolution of, 103-­115
Cell-type-specific gene expression, 112
Cenancestor, 37
Cephalochordata, 198­-203
Cercopithecoidea, 231
Chagas disease, 28, 269-­270
Chance occurrence, 9­10, 31
Channelopathy, 127
Charcot-Marie-Tooth disease, 261
CHARGE syndrome, 57
Chemical diversity, 154
Chemokine, 293, 301
Child class, 198
Chimeric Antigen Receptor for T cells (CAR-T) therapy, 157, 164
Chitin, 185
Chlamydia trachomatis, 292
Chloroplast evolution, 14­15, 17, 31
Choanoflagellatea, 186­187
Choanozoa. See Apoikozoa Chondrichthyes, 215
Chordata, 197­203
Chordoma, 198
Choriocarcinoma, 221
Chromatin, 156
Chromosomal disorder, 271
Chromosomes, 61
  number, variations in, 66
Chronic obstructive pulmonary disease (COPD), 271
Chytrids, 186
Cichlids, 153­154, 154f Ciliopathies, 213-­214, 233
Cis-acting vs. trans-acting, 127-­128
CISD2 gene, 264
Cisd2-null mice, 264
Clade, 128
Cladistics, 198
Class, 7, 32
  of animals, 10, 12, 24­-25 
  of cells, 6 
  of metazoan organisms, 25 
  of organisms, 4­5 
  of paradoxes, 5
Classification, 11 
  data retrieval, 176 vs. diagnosis, 199 
  flying animals, 175 
  formal definition of, 175 
  inferencing, 176 
  mammals, Aristotle, 173-­174 vs. ontology, 177, 198 
  pseudo-scientific assertion, 177 
  self-correction, 177 
  simplification, 175 swimming animals, 175 walking animals, 175
Classification system vs. identification system, 325
Class noise, 322. See also Blended class Clinical trial, 286-­287, 301
Clostridium feseri (blue bacteria), 107f 
Clustered Regularly Interspaced Short
  Palindromic Repeats (CRISPR), 251
Cnidaria, 193
Cnidarian organisms, 193, 195f Coccidia, 28
Cockayne syndrome, 262
Codon, 8, 32
Cofactor, 156, 165
Collision tumor theory, 120
Colon cancers, 119
Combined deficiency, 128
Commensal, 32­33
Competence of classification, 176
Complex disease, 33
Composition theory, 120
Congenital anomaly, 271
Congenital chondrodystrophy, 17-­18
Congenital disorder, 17-­18, 33
Congenital hemangiomas, 119
Connective tissue, 128
Contig disease, 271
Contiguous gene deletion syndrome, 271
Convergence, 165
Conversion theory, 120
Copy number, 78
Corbels, 239-­240
Cornelia de Lange syndrome, 112
Corpus callosum, 222
Cousin class, 167
CpG island, 128
CpG sites, 103
Cranial neural crest, 208
Craniata, 128, 148-­149, 198­-203, 207-­212
Craniates. See Craniata Crocodilia, 218
Crohn's disease, 273
Ctenophora, 193
Ctenophorans, 193, 194f Cyanobacteria, 14­15, 15f, 17, 23, 33
Cyclic neutropenia, 55
Cyclostomata, 211-­212
Cynodonts, 219
Cystic fibrosis transmembrane conductance regulator (CFTR), 113
Cytokine storm, 286-­287
Cytopenia, 78
Cytotrophoblasts, 229


D 
Danio rerio (zebrafish), 294, 297­-298, 298f Daphnia pulex, 154
Darwin's theory, 153
Decitabine, 122 delta1-Crystallin, 18
Demodex, 291
Demospongiae, 192
De novo disease mutations, 56-­58
De novo genes, 74­-76
De novo mutation, 78
Dense core granules, 210
Dermal bones, 209
Dermis, 255
Dermoptera, 230
Desmosomes, 187, 188f, 189, 190f, 191
Deuterostomia, 197
Deuterotomia, 148-­149
Developmental disorder, 128
Devolution, 241
Diagnosis vs. classification, 199
Diamond Blackfan anemia, 210
Diethystilbestrol (DES), 117
Differentiation, 78
Digenic disease, 128­-129
DiGeorge syndrome, 82
Dinosauria, 218
Diploid organism, 7
Dipnomorpha, 216
Dipnotetrapodomorpha, 216
Dipoblasts, 193
Direct mutagen, 52
Direct transdifferentiation, 111
DNA, 73­87
DNA-DNA reassociation kinetics, 151-­152
DNA methylation, 4, 33
DNA repair, 17, 33
Dollo's law, 271
Dormancy, 33
Down syndrome, 56
Driver pathway, 19, 34
Drosophila melanogaster, 101, 294, 297
Drug development, economics of, 20
Druggable driver, 34
Dysgerminomas in women, 102
Dyskeratosis congenita, 262
Dysplasia, 199


E 
Echidnas, 226
Echinodermata, 197
Ectoderm, 129
Eikenella corrodens, 289
Embryo, 99­103 vs. fetus, 129
Embryogenesis, 161
Embryology, relationship between evolution and, 93-­103
Embryonic anlagen, 102
Embryonic stem cell, 129
Endoderm, 6, 34
End-stage condition, 272
Enhancer, 78
Enigmatic pacific hagfish, 211-­212, 212f 
Enterocoelomata. See Deuterostomia Epidermis, 255, 256f 
Epigenome, 4, 34, 221
Epigenome disruptors, 121-­122
Epigenomic methylation, variations in, 65
Epimutation, 129-­130
Epipubic bones, 239
Epistasis, 34­35
Epithelial cell, 130
Epitheliozoa, 193
Epithelium, 189, 189f Erasure, 105-­106, 221
ERCC6 gene, 262
ERCC8 gene, 262
Etiology, 79
Euarchonta, 230
Euarchontoglires, 229-­230
Eugenics, 247-­252
Eugnathostomata, 215
Eukaryota, 15, 148­149
  Bikonta, 183-­184 eukaryotes, 179
  Excavata, 183-­184 
  mitochondria, 180 
  nucleus, 179, 182
  Podiata, 183­184 
  prokaryotic life forms, 179 
  single-celled eukaryotes, 179, 180f 
  Syringammina fragilissima, 179 
  undulipodia, 182
  Unikonta, 183-­184
Eukaryotes, 7, 67, 153­-155, 161, 176, 189
Eumetazoa, 191-­193
Euteleostomi, 215
Eutheria, 97-­98, 226-­235
Eutherians, 226-­235
Evo-devo, 130
Evolutionary convergence, 166
Evolutionary frustration, principle of, 248
Evolution, 
  as fantasy bacterial pathogen, 317­-319 
  disease diagnosis by symptoms, 321­-323 
  drug development and testing, 319 
  homologous genes, 316­317 
  science fiction aficionados, 324 
  speciation, 324 
  taxonomic organisms, treatments for, 319-­321 
  theory of intelligent design, 324-­326
Evolution deniers, 307
Evolvability, 153, 165
Exaptation, 35
Excavata, 183­184, 290
Exome sequencing, 79
Extraembryonic cells, 233
Extraembryonic tissues, 221, 233


F 
Facultative intracellular organism, 79
Fanconi anemia bone marrow failure, 257, 263
Female Anopheles mosquito, 107
Fetal period, 101
Filarial nematodes, 292
Filozoa, 186
First Law of Bioinformatics, 59
Fish, 118-­119
Forme fruste, 130
Founder effect, 13, 35
FOXL2 gene, 112
Fungi, 28, 186, 189


G 
Gallertoids, 130, 187, 191­192
Gametes, 6, 35, 148­-149
Gametic organism, 7
Gametophytes, 7
Gastrointestinal stromal tumors (GISTs), 19
Gastropods, 118-­119
Gene(s), 269
Gene conservation, 58-­61
Gene diversity, 154
Gene editing techniques, 251
Gene pool, 13, 26, 35, 58­61, 151­152, 314, 317­319, 324
Generalization, 35
Gene regulation, 35
Gene sharing, 18
Gene size, 66­67
Gene-targeted therapy, 19
Genetically engineered mouse (GEM), 233-­234
Genetic fine-tuning, 124­-138
Genetic heterogeneity, 130
Genetic instability, 79
Genetic mutations, 151
Genetic surplus disorder, 79
Genome, 12, 14-­15, 26, 35
Genome Wide Association Study (GWAS), 272
Genomic architecture, 64­73
Genomic disorder, 79
Genomic regulation, 76­87
Genomic regulatory processes, 125­138
Genomic regulatory systems, 
  pathologic conditions of, 121-­138
Genomic structural abnormalities (GSVs), 69
Genomic structural variation, 79
Germ cell, 6, 35
Germ cell line, 35­-36
Germ layers, 131
Germline, 79
Germline mutation, 80
Gestational trophoblastic disease, 234
Giant viruses, 162
Glires, 230
Globins, 13
Gnathostomata, 161, 214-­215
Gorillini, 232


H 
HACEK, 272
Haeckel's theory, 96-­97
Haemophilus influenzae, 244
Hair follicles, 223­224, 224f Hamartoma, 158, 166
Haploid, 7­8, 36
Haploid organisms, 7, 36
Haplorrhini/haplorhini, 231
Haplotype, 80
HAS2 gene, 248
Hemichordata, 197
Hepatitis B, 292
Hepatocyte, 100
Hepatoid adenomas, 119
Hepatoma, 131
Hereditary nonpolyposis colorectal cancer syndrome, 131
Heritability, 131
Heterokonts, 289, 301
Hirschspring disease, 209
Histone, 65, 199
Histone disruptors, mild effects of, 122
Histopathology, 131
Histozoa, 193
Hodgkin lymphoma, 273
Holometabolism, 156, 166
Holomycota, 186
Holozoa, 186
Holt-Oram syndrome, 123
Homeobox, 36
Hominidae, 231­232
Homininae, 232
Hominini, 232
Hominoidea, 231
Homo, 232
Homo erectus, 232
Homolog, 12, 18, 24, 36
Homologous genes, 316-­317
Homologous recombination, 
  during meiosis, 62
Homoplasy, 166
Homo sapiens, 147­149, 176, 232­235
Homozygosity, 80
Hookworms, 292
Horizontal gene transfer, 80
Horse, 
  gestation period of, 241f 
Horseshoe crabs, 149, 149f 
Host, 155­157, 159­161, 163, 166
HOX gene diseases, mild clinical course of, 123
HOX genes, 24
Human(s), 232­235
Human diseases, 115­118
Human embryo, dorsum of, 97f Human embryology, 246
Human embryonic stem cells, 100f Human gene pool, 55-­56
Human kidney, 101
Human phylogenetic lineage, 177­-179
Hutchinson-Gilford progeria syndrome, 263
Hydatidiform mole, 221, 234
Hydractinia carnea, 253
Hydrops-ectopic calcification-"moth-eaten" (HEM), 17-­18
Hylobatidae, 231
Hyperplasia, 273
Hypoxanthine-guanine phosphporibosyl transferase (HGPRT), 60­-61

Evolution’s Clinical Guidebook: Translating Ancient Genes Into Precision Medicine is available from Amazon or from the publisher's website. If you are fortunate enough to have full institutional access to ScienceDirect, you can download chapters at no cost.

Jules Berman

key words: evolution, precision medicine, genetics, rare disease, clinical genetics, bioinformatics, evo-devo, Jules J. Berman, Ph.D., M.D.

Contents: Evolution’s Clinical Guidebook: Translating Ancient Genes Into Precision Medicine

In yesterday's blog, I announced the publication of my book, Evolution’s Clinical Guidebook: Translating Ancient Genes Into Precision Medicine. The premise of this book is that modern medicine is based on an understanding of evolutionary processes. Basically, without evolution, the fledgling field of precision medicine would wither and die, and we would lose our opportunity to prevent, diagnose, and treat the diseases that account for the bulk of morbidity and mortality in humans and in animals.

This book is available from Amazon or from the publisher's website. If you are fortunate enough to have full institutional access to ScienceDirect, you can download chapters at no cost. Here is the Table of Contents.

Contents: Evolution’s Clinical Guidebook: Translating Ancient Genes into Precision Medicine

1. Evolution, From the Beginning 1

Section 1.1 In the Beginning 1
Section 1.2 Bootstrapping Paradoxes 5
Section 1.3 Our Genes, for the Most Part, 
Come From Ancestral Species 12
Section 1.4 How do Metabolic Pathways Evolve? 15
Section 1.5 Cambrian Explosion 21
Section 1.6 After the Cambrian: Coexistence 
and Coevolution 25
Glossary 29
References 44

2. Shaking Up the Genome 51
Section 2.1 Mutation Burden 51
Section 2.2 Gene Pools and Gene Conservation 58
Section 2.3 Recombination and Other 
Genetic Tricks 61
Section 2.4 Genomic Architecture: 
An Evolutionary Free-for-All 64
Section 2.5 Rummaging Through the DNA Junkyard 73
Glossary 77
References 87

3. Evolution and Embryonic Development 93
Section 3.1 The Tight Relationship Between 
Evolution and Embryology 93
Section 3.2 The Epigenome and the Evolution 
of Cell Types 103
Section 3.3 An Embryonic Detour for 
Human Diseases 115
Section 3.4 The Borderland of Embryology 
and Cancer 118
Section 3.5 Pathologic Conditions of the 
Genomic Regulatory Systems 121
Glossary 125
References 138

4. Speciation 145
Section 4.1 A Species is a Biological Entity 145
Section 4.2 The Biological Process of Speciation 147
Section 4.3 The Diversity of Living Organisms 152
Section 4.4 The Species Paradox 157
Section 4.5 Viruses and the Meaning of Life 159
Glossary 164
References 168

5. Phylogeny: Eukaryotes to Chordates 173
Section 5.1 On Classification 173
Section 5.2 The Complete Human 
Phylogenetic Lineage 177
Section 5.3 Eukaryotes to Obazoans 179
Section 5.4 Opisthokonts to Parahoxozoa 185
Section 5.5 Bilaterians to Chordates 193
Glossary 198
References 203

6. Phylogeny: Craniates to Humans 207
Section 6.1 Class Craniata and the Ascent 
of the Neural Crest 207
Section 6.2 Vertebrates to Synapsids 212
Section 6.3 Mammals to Therians 220
Section 6.4 Eutherians to Humans 226
Glossary 233
References 235

7. Trapped by Evolution 239
Section 7.1 Spandrels, Pendentives, Corbels, 
and Squinches 239
Section 7.2 Evolving Backwards 240
Section 7.3 Eugenics: Proceed With Caution 247
Section 7.4 The Evolution of Aging, 
and the Diseases Thereof 252
Section 7.5 Why Good People Get Bad Diseases 265
Glossary 270
References 277

8. Animal Models of Human Disease: Opportunities 
and Limitations 285
Section 8.1 The Animal Model Problem, in a 
Nutshell 285
Section 8.2 Specificities and Idiosyncrasies 286
Section 8.3 New Animal Options 294
Section 8.4 The Proper Study of Mankind 300
Glossary 301
References 302

9. Medical Proof of Evolution 307
Section 9.1 What Does Proof Mean, 
in the Biological Sciences? 307
Section 9.2 The Differences Between Designed 
Organisms and Evolved Organisms 309
Section 9.3 What if Evolution Were Just 
a Foolish Fantasy 316
Glossary 325
References 326
Index 329

Jules Berman

key words: evolution, precision medicine, genetics, rare disease, clinical genetics, bioinformatics, evo-devo, Jules J. Berman, Ph.D., M.D.

Just Published: Evolution’s Clinical Guidebook: Translating Ancient Genes Into Precision Medicine

This month, Academic Press has published my book, Evolution’s Clinical Guidebook: Translating Ancient Genes Into Precision Medicine. The premise of this book is that modern medicine is based, in one way or another, on an understanding of evolutionary processes. If evolution were a fabrication, then we would not be able to make any sense of the genomic data that is pouring out of research laboratories. We would not be able to design rational, cost effective, screening protocols to test the effectiveness of new drugs. We would not be able to identify the human sub-populations that will benefit from gene-targeted therapies. We would not be able to find the cause of rare diseases, and we would not be able to apply such knowledge to the treatment of common diseases. Without evolution, we would not understand how cancer develops, or how we might intervene in the process. Basically, without evolution, the fledgling field of precision medicine would wither and die, and we would lose our opportunity to prevent, diagnose, and treat the diseases that account for the bulk of morbidity and mortality in humans and in animals. This book demonstrates, through hundreds of examples, that modern medicine is built on the theory of evolution.

This book is available from Amazon or from the publisher's website. If you are fortunate enough to have full institutional access to ScienceDirect, you can download chapters at no cost.

Jules Berman

key words: evolution, precision medicine, genetics, rare disease, clinical genetics, bioinformatics, evo-devo, Jules J. Berman, Ph.D., M.D.

Inscrutable Genes

• "In most cases, the molecular consequences of disease, or trait-associated variants for human physiology, are not understood." from: Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature 2009;461:747–53.

The 1960s was a wonderful decade for the field of molecular genetics. Hundreds of inherited metabolic diseases were being studied. Most of these diseases could be characterized by a simple inherited mutation in a disease-causing gene. Back then, we thought we understood genetic diseases. Here’s how it all might have worked, if life were simple: one mutation! one gene ! one protein ! one disease. This lovely genetic parable, from a bygone generation, seldom applies in the era of Precision Medicine. The purpose of this section is to explain some of the complexities of modern genetics and to lay out the job of the Precision Medicine scientist who must dissect the pathways that lead from gene to disease.

In Precision Medicine and the Reinvention of Human Disease, two of the most confuding aspects of modern disease genetics are discussed: that a single disease may result from one of many distinct molecular defects; and that a single gene may produce many different diseases. These two countervailing phenomena tell us something very important about disease development. The first is that different pathways may converge to the same disease, and that any single gene may perturb a biological system (i.e., a living organism) in different ways. Some of that discussion is excerpted here.

There are numerous examples wherein mutations in one gene may result in more than one disease [2]. In some cases, each of the diseases caused by the altered gene is fundamentally similar (e.g., spherocytosis and elliptocytosis, caused by mutations in the alpha-spectrin gene; Usher syndrome type IIIA and retinitis pigmentosa-61 caused by mutations in the CLRN1 gene). In other case, diseases caused by the same gene may have no obvious relation to one another. For example, the APOE gene encodes apolipoprotein E, which is involved in the synthesis of lipoproteins. One common allele of the APOE locus, e4, increases the risk of Alzheimer disease and of heart disease, two disorders of no obvious clinical similarities [3,4].

Let’s look at a few other examples where mutations in a single gene play causal roles in the development of diverse diseases. For example, different mutations of the same gene, desmoplakin, cause the following diseases [2]:

• Arrhythmogenic right ventricular dysplasia 8

• Dilated cardiomyopathy with woolly hair and keratoderma

• Lethal acantholytic epidermolysis bullosa

• Keratosis palmoplantaris striata II

• Skin fragility-woolly hair syndrome

How is it possible that errors in the gene coding for desmoplakin, a constituent protein found in intercellular junctions, could account for such apparently unrelated diseases as arrhythmogenic right ventricular dysplasia and lethal acantholytic epidermolysis bullosa? It happens that we know that specialized desmosomes in cardiac cells (i.e., intercalated discs) tightly couple myocytes so that they can function as a coordinated group. Desmosomes are also required to adhese skin epidermal cells to one another and to the underlying basement membrane. In the case of desmoplakin mutations, it is relatively easy to see the pathogenetic relationship among these diseases.

In other sets of diseases that result from an error in one specific gene, the pathogenetic relationship may not be so easily discerned. Some cases of Charcot-Marie-Tooth axonal neuropathy, lipodystrophy, Emery-Dreyfus muscular dystrophy, and premature aging syndromes are all caused by mutation in the LMNA (Lamin A/C) gene. Stickler syndrome type III, Fibrochondrogenesis-2, and a form of nonsyndromic hearing loss are all caused by mutations in the COL11A2 gene. In these cases, how can variations in a single gene cause many different diseases?

Let’s look at just a few of the possibilities:

• One gene can control the synthesis of more than one protein [6].

• A single protein may have multiple functions. For example, nuclear lamina (lamin a/c) has several biological roles: controlling nuclear shape, influencing transcription, and organizing heterochromatin. Mutations in the LMNA gene cause more than 10 different clinical syndromes, including neuromuscular and cardiac disorders, premature aging disorders, and lipodystrophy. Likewise, the polyfunctional TP53 gene has been linked to 11 clinically distinguishable cancer-related disorders [7].

• A single protein with a single function may have different biological effects based on the cell type in which the protein is expressed, the stage of development in which the protein is expressed, and the cellular milieu (e.g., concentrations of substrate or protein inhibitors) for a given cell type, at a particular moment in time.

• Diseases develop through a sequence of biological events occurring over time. A mutation may exert a different biological effect based on where and when, in the sequence of pathogenetic events, it is expressed.

more to follow

- Jules Berman

key words: precision medicine, genetics, multi-step, pathogenesis, genetic heterogeneity, jules j berman Ph.D. M.D.

Genes that Cause More Than One Disease

Rare Disease Day is coming up February 29 (a rare day for rare diseases). In honor of the upcoming event, I'll be posting blogs related to the rare diseases.

There are numerous examples wherein mutations in one gene may result in more than one different diseases, usually depending on the mutation involved. In some cases, each of the diseases caused by the altered gene are fundamentally similar (e.g., spherocytosis and elliptocytosis, caused by mutations in the alpha-spectrin gene; Usher syndrome type IIIA and retinitis pigmentosa-61 caused by mutations in the CLRN1 gene). In other case, diseases caused by the same gene may have no obvious relation to one another. For one example, diverse diseases that include Charcot-Marie-Tooth axonal neuropathy, lipodystrophy, Emery-Dreyfus muscular dystrophy, and premature aging syndromes, are all caused by mutation in the LMNA (Lamin A/C) gene. As another example, Stickler syndrome type III (STL3), Fibrochondrogenesis-2 and a form of non-syndromic hearing loss are all caused by mutations in the COL11A2 gene.

What is the significance of these observations? It tells us that it may be impossible to create a gene-based classification of diseases. Think about it: How can you group diseases by causal gene when the diseases caused by the gene are otherwise unrelated? It also tells us that there is a great deal that we do not understand about how genes cause diseases.

In the following list, each disease-causing gene is followed by the different diseases caused by gene alterations.

ABCB6 gene
The Lan(-) blood group phenotype
Microphthalmia, isolated, with coloboma 7

ACTA2 gene
Moyamoya disease-5
Form of thoracic aortic aneurysm

ACYLTRANSFERASE GENE
Fish-eye disease
Norum disease

ALPHA-SPECTRIN GENE
Hereditary spherocytosis-3
Elliptocytosis-2

ALPHA-SYNUCLEIN GENE
Parkinson disease-1
Autosomal dominant Parkinson disease-4

ALX4 gene
Frontonasal dysplasia-2
Parietal foramina-2

ANO5 gene
Gnathodiaphyseal dysplasia; gdd, or osteogenesis imperfecta with unusual skeletal lesions
Limb-girdle muscular dystrophy-2L
Miyoshi muscular dystrophy-3

ARX gene
Proud syndrome
Form of nonspecific X-linked mental retardation

ATN1 gene
Dentatorubral-pallidoluysian atrophy
Haw River syndrome

ATR gene
Seckel syndrome-1
Form of ataxia telangiectasia

BAG3 gene
Autosomal dominant myofibrillar myopathy
Dilated cardiomyopathy-1HH

BAP1 gene
Susceptibility to uveal melanoma
Predisposition to malignant mesothelioma upon asbestos exposure

BCS1L gene
Bjornstad syndrome
GRACILE syndrome

BUB1B gene
Mosaic variegated aneuploidy syndrome-1 (See Glossary item, Aneuploidy)
Form of premature chromatid separation

C20ORF54 gene
Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness
Fazio-Londe disease

CACNA1A gene
Familial hemiplegic migraine
Spinocerebellar ataxia 6

CACNA1F gene
X-linked cone-rod dystrophy-3
Aland Island eye disease

CARD15 gene
Early-onset sarcoidosis
Blau syndrome

CASK gene
FG syndrome-4 ("FG" are the initials of the first proband)
Mental retardation, x-linked, with or without nystagmus
Mental retardation and microcephaly with pontine and cerebellar hypoplasia

CAVEOLIN-3 GENE
Limb-girdle muscular dystrophy type 1C
Tateyama type of distal myopathy

CEP152 gene
Autosomal recessive primary microcephaly-4
Seckel syndrome-5

CEP290 gene
Bardet-Biedl syndrome 14
Joubert syndrome 5
Leber congenital amaurosis 10
Meckel syndrome 4
Senior-Loken syndrome 6

CHAT (Choline acetyltransferase) gene
Presynaptic congenital myasthenia syndrome with episodic ataxia
Familial infantile myasthenia gravis

CHX10 gene

Microphthalmia, isolated-2
Microphthalmia with coloboma-3
Isolated colobomatous microphthalmia-3

CLCN5 gene
X-linked recessive hypophosphatemic rickets
X-linked recessive nephrolithiasis with renal failure
Dent disease-1

CLN8 gene
Neuronal ceroid lipofuscinosis-8
Progressive epilepsy with mental retardation

CLRN1 gene
Usher syndrome type IIIA
Retinitis pigmentosa-61

COL11A2 gene
Stickler syndrome type III
Fibrochondrogenesis-2
Form of nonsyndromic hearing loss

COL2A1 gene
Stickler syndrome type I, sometimes called membranous vitreous type
Osteoarthritis with mild chondrodysplasia
Achondrogenesis type II
Czech dysplasia

COL7A1 gene
Classic dystrophic epidermolysis bullosa pruriginosa
Nonsyndromic congenital nail disorder-8

COL9A1 gene
Form of autosomal recessive form of Stickler syndrome
Multiple epiphyseal dysplasia-6

COL9A2 gene
Multiple epiphyseal dysplasia-2
Stickler syndrome type V

COLLAGEN GENE
Autosomal dominant epidermolysis bullosa dystrophica
Pretibial dystrophic epidermolysis bullosa
Stickler syndrome
Strudwick type of spondyloepimetaphyseal dysplasia
Spondyloperipheral dysplasia
Ehlers-Danlos syndrome type IV

CONNEXIN-26 GENE
Keratitis-ichthyosis-deafness syndrome
Deafness, autosomal dominant-3A

CRYAB gene
Posterior polar cataract-2
Fatal infantile hypertonic myofibrillar myopathy

CYLD gene
Familial cylindromatosis
Multiple familial trichoepithelioma-1
Brooke-Spiegler syndrome

DOCK8 gene
Hyper-IgE recurrent infection syndrome, also known as Job syndrome
Autosomal dominant mental retardation-2

DYM gene
Dyggve-Melchior-Clausen disease
Smith-McCort dysplasia

DYNC1H1 gene
Autosomal dominant axonal Charcot-Marie-Tooth disease type 2O
Autosomal dominant mental retardation-13

ENPP1 gene
Generalized arterial calcification of infancy-1
Autosomal recessive hypophosphatemic rickets-2

ESCO2 gene
SC phocomelia syndrome, also known as SC pseudothalidomide syndrome
Roberts syndrome

FBLN5 gene
Autosomal recessive cutis laxa type IA
Macular degeneration, age-related-3

FBN1 gene
Acromicric dysplasia
Stiff skin syndrome
Autosomal dominant form of isolated ectopia lentis
Weill-Marchesani syndrome-1
Weill-Marchesani syndrome-2
Geleophysic dysplasia-2

FGFR1 gene
Trigonocephaly-1
8p11 myeloproliferative disorder

FGFR2 gene
Beare-Stevenson cutis gyrata syndrome
Form of craniosynostosis
Classic Crouzon syndrome

FGFR3 gene
Muenke craniosynostosis syndrome
Hypochondroplasia
CATSHL syndrome
Crouzon syndrome with acanthosis nigricans

FIG4 gene
Charcot-Marie-Tooth type 4J
Form of autosomal dominant ALS
Amyotrophic lateral sclerosis 11

FLNA gene
Terminal osseous dysplasia
FG syndrome-2
X-linked cardiac valvular dysplasia

FLNC gene
Filamin C-related myofibrillar myopathy
Distal myopathy-4 (MPD4), also known as Williams distal myopathy

FMR1 gene
Fragile X tremor/ataxia syndrome
Fragile X mental retardation syndrome

FOXL2 gene
Blepharophimosis, ptosis, and epicanthus inversus syndrome, with premature ovarian failure (BPES type I)
Blepharophimosis, ptosis, and epicanthus inversus syndrome, without premature ovarian failure without premature ovarian failure (BPES type II)

FREM1 gene
Bifid nose with or without anorectal and renal anomalies
Trigonocephaly-2

GATA2 gene
Primary lymphedema with myelodysplasia
Dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency

GDAP1 gene
Autosomal recessive axonal CMT with vocal cord paresis
Autosomal recessive demyelinating CMT4A
Autosomal recessive axonal Charcot-Marie-Tooth disease type 2K

GDF3 gene
Klippel-Feil syndrome-3
Isolated microphthalmia with coloboma-6
Isolated microphthalmia-7

GDF6 gene
Klippel-Feil syndrome-1
Isolated microphthalmia-4

GJA1 gene
Syndactyly type III
Oculodentodigital dysplasia
Atrioventricular septal defect 3

GJB2 gene
Autosomal recessive deafness-1A
Hystrix-like ichthyosis-deafnesss syndrome

GJC2 gene (encodes gap junction protein, gamma 2)
Autosomal recessive spastic paraplegia-44
Hereditary lymphedema type IC
Form of Pelizaeus-Merzbacher disease

GLUCOKINASE GENE
Familial hyperinsulinemic hypoglycemia-3
Maturity onset diabetes of the young-2

GNAS gene
Progressive osseous heteroplasia
Pseudopseudohypoparathyroidism
Pseudohypoparathyroidism type Ia

GPR143 gene
Ocular albinism type I
X-linked congenital nystagmus-6
Nystagmus 6, congenital, X-linked

HCN4 gene
Brugada syndrome-8
Autosomal dominant form of sick sinus syndrome

HEDGEHOG GENE
Holoprosencephaly-3
Isolated microphthalmia with coloboma-5

HPRT gene
Lesch-Nyhan syndrome
Kelley-Seegmiller syndrome

HRG gene
Histidine-rich glycoprotein deficiency
Thrombocythemia-11

HSPB8 gene
HMN2A
Axonal Charcot-Marie-Tooth disease type 2L
HMN2A

IGHMBP2 gene
Distal hereditary motor neuronopathy type VI (dHMN6 or HMN6)
Spinal muscular atrophy, with respiratory distress-1

INF2 gene
FSGS5
Focal segmental glomerulosclerosis-5
Charcot-Marie-Tooth disease E with focal segmental glomerulonephritis

JAK2 gene
Thrombocythemia-3
Polycythemia vera, the most common form of primary polycythemia

KCNE2 gene
ATFB4
Form of atrial fibrillation
Long QT syndrome-6

KCNH2 gene
Long QT syndrome-2
Short QT syndrome-1

KCNJ11 gene
Hyperinsulinemic hypoglycemia-2 (HHF2)
TNDM3

KCNJ5 gene
Familial hyperaldosteronism type III
Long QT syndrome-13

KCNQ1 gene
Form of Jervell and Lange-Nielsen syndrome (JLNS1)
Form of autosomal dominant atrial fibrillation
ATFB3 (607554)
Short QT syndrome-2

KIF1A gene
Hereditary sensory neuropathy type IIC
Form of mental retardation

KLF1 gene
Congenital dyserythropoietic anemia type IV (See Glossary item, Dyserythropoiesis)
Form of hereditary persistence of fetal hemoglobin

KRT74 gene
Hypotrichosis simplex of the scalp-2
Autosomal dominant form of woolly hair
Hypotrichosis simplex of the scalp-2

LDB3 gene
Left ventricular noncompaction-3
Form of dilated cardiomyopathy with or without left ventricular noncompaction

LMNA gene
Form of autosomal recessive axonal CMT
Slovenian type heart-hand syndrome

LRP4 gene
Cenani-Lenz syndactyly syndrome
Sclerosteosis-2

LRP5 gene
Familial exudative vitreoretinopathy-4
Autosomal dominant osteopetrosis type I

MATRILIN-3 GENE
Form of multiple epiphyseal dysplasia
Form of autosomal recessive spondyloepimetaphyseal dysplasia

MECP2 gene
Form of neonatal severe encephalopathy
Classic Rett syndrome

MED12 gene
Lujan-Fryns syndrome
Opitz-Kaveggia syndrome, also known as FG syndrome-1

MFRP gene
Posterior microphthalmia, retinitis pigmentosa, foveoschisis, and optic disc drusen
MCOP5

MLL2 gene
Kabuki syndrome-1
Otitis media in infancy

MSX1 gene
Form of selective tooth agenesis
Orofacial cleft 5
Witkop syndrome

MYH6 gene
Familial hypertrophic cardiomyopathy-14
Form of dilated cardiomyopathy

MYH7 gene
Form of scapuloperoneal myopathy
Hypertrophic cardiomyopathy-1
Cardiomyopathy, dilated, 1S

MYH9 gene
Fechtner syndrome
May-Hegglin anomaly
Sebastian syndrome

NEMO gene
Anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis, and lymphedema
Atypical mycobacteriosis, familial
Familial incontinentia pigmenti
Invasive pneumococcal disease, recurrent isolated, type 2

NF1 gene
Neurofibromatosis-1
Watson syndrome
Neurofibromatosis-Noonan syndrome variant of neurofibromatosis-1

NHS gene
Nance-Horan syndrome
X-linked congenital cataract

NKX2-5 gene
Atrial septal defect of the secundum type, with or without atrioventricular conduction defects
Congenital nongoitrous hypothyroidism-5
Hypoplastic left heart syndrome-2

NOTCH2 gene
Hajdu-Cheney syndrome
Alagille syndrome-2

NPHP1 gene
Senior-Loken syndrome-1
Form of Joubert syndrome plus nephronophthisis

NPHP3 gene
Meckel syndrome, type 7
Nephronophthisis-3

NPHP4 gene
Form of Senior-Loken syndrome that maps to 1p36
Type 4 nephronophthisis

NPHP6 gene
Form of Senior-Loken syndrome that maps to 12q21-32
Joubert syndrome-5

NR0B1 gene
X-linked congenital adrenal hypoplasia with hypogonadotropic hypogonadism
46,XY sex reversal-2

NR5A1 gene
Premature Ovarian Failure-7
Form of 46,XY sex reversal

NRAS gene
Form of Noonan syndrome (NS6)
Form of autoimmune lymphoproliferative syndrome, designated type IV (ALPS4)

NSD1 gene
Familial Sotos syndrome
Sotos syndrome
Weaver syndrome-1
Classic Sotos syndrome

OPTN gene
Amyotrophic lateral sclerosis-12
Form of adult-onset primary open angle glaucoma (POAG), designated GLC1E

P63 GENE
Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome-3
Split-hand/split-foot malformation

PAX3 gene
Craniofacial-deafness-hand syndrome
Waardenburg syndrome type-3
Waardenburg syndrome type-1

PDE6B gene
Autosomal dominant congenital stationary night blindness-2
Form of retinitis pigmentosa

PDE8B gene
Autosomal dominant striatal degeneration
Primary pigmented nodular adrenocortical disease-3

PDX1 gene
Congenital pancreatic agenesis
Maturity onset diabetes of the young-4

PIGA gene
Paroxysmal nocturnal hemoglobinuria
Multiple congenital anomalies-hypotonia-seizures syndrome-2

PLA2G6 gene
Neurodegeneration with brain iron accumulation-2A
Neurodegeneration with brain iron accumulation-2B
Adult-onset dystonia-parkinsonism, also known as Parkinson disease-14

PLEC1 gene
Epidermolysis bullosa simplex with pyloric atresiawhich
Epidermolysis bullosa simplex
Autosomal recessive limb-girdle muscular dystrophy type 2Q

POLG gene
Alpers syndrome
Neurogastrointestinal encephalopathy

POLYMERASE-GAMMA GENE
Autosomal recessive progressive external ophthalmoplegia (PEOB)
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis

POMGNT1 gene
Walker-Warburg syndrome (WWS) or muscle-eye-brain disease
Muscular dystrophy-dystroglycanopathy-B3
Muscular dystrophy-dystroglycanopathy-C3

PRKAR1A gene
Acrodysostosis with hormone resistance
Carney complex, type 1

PROM1 gene
Macular dystrophy, retinal, type 2
Stargardt disease-4

PROMININ-1 GENE
Stargardt disease-4
Retinal macular dystrophy-2
Cone-rod dystrophy-12

PRPS1 gene
Arts syndrome
X-linked deafness-1

PRRT2 gene
Familial infantile convulsions with paroxysmal choreoathetosis
Benign familial infantile seizures-2
Paroxysmal kinesigenic dyskinesia

PSEN1 gene
Dilated cardiomyopathy-1U
Familial acne inversa-3
Form of early onset Alzheimer's disease

PTPN11 gene
Noonan syndrome-1
Metachondromatosis

PYCR1 gene
Autosomal recessive cutis laxa type IIIB
Autosomal recessive cutis laxa type IIB

RAB27A gene
Melanosis with immunologic abnormalities with or without neurologic impairment
Griscelli syndrome type 2

RAF1 gene
Form of Noonan syndrome
LEOPARD syndrome-2

RDS gene
Retinitis pigmentosa-7
Adult-onset vitelliform macular dystrophy (AVMD)

RET gene
Susceptibility to Hirschsprung disease-1
Multiple endocrine neoplasia-2B
Familial medullary thyroid carcinoma MTC

ROR2 gene
Brachydactyly type B1
Autosomal recessive Robinow syndrome

RPE65 gene
Leber congenital amaurosis-2
Form of autosomal recessive retinitis pigmentosa

RPGR gene
Retinitis pigmentosa-3
X-linked cone-rod dystrophy
X-linked retinitis pigmentosa with recurrent respiratory infections

RPGRIP1 gene
Autosomal recessive cone-rod dystrophy-13
Leber congenital amaurosis-6

SAMHD1 gene
Aicardi-Goutieres syndrome-5
Chilblain lupus-2

SCN1A gene
Febrile seizures, familial, type 3A
Familial hemiplegic migraine-3

SCN1B gene
Generalized epilepsy with febrile seizures plus, type 1
Brugada syndrome-5

SCN2A gene
Benign familial neonatal-infantile seizures-3
Early infantile epileptic encephalopathy-11

SCN4A gene
Hypokalemic periodic paralysis type 2
Form of congenital myasthenic syndrome

SCN5A gene
Brugada syndrome-1
Long QT syndrome-3
Sick sinus syndrome (some cases)
Atrial fibrillation, (some cases)
Dilated cardiomyopathy (some cases)

SEMA4A gene
Form of RP
Cone-rod dystrophy-10

SH3TC2 gene
Charcot-Marie-Tooth disease type 4C
Mild mononeuropathy of the median nerve

SHH gene
Holoprosencephaly-3
Microphthalmia with coloboma 5

SLC16A1 gene
Erythrocyte lactate transporter defect
Form of hyperinsulinemic hypoglycemia

SLC25A19 gene
Amish lethal microcephaly
Thiamine metabolism dysfunction syndrome-3
Bilateral striatal degeneration and progressive polyneuropathy

SLC26A4 gene
Enlarged vestibular aqueduct
Pendred syndrome

SLC2A1 gene
Dystonia 18 (DYT18)
Autosomal recessive primary hypertrophic osteoarthropathy-2

SLC33A1 gene
Spastic paraplegia-42
Congenital cataracts, hearing loss, and neurodegeneration

SLC34A1 gene
Autosomal recessive form of Fanconi renotubular syndrome
Hypophosphatemic nephrolithiasis/osteoporosis-1
Fanconi renotubular syndrome-2

SLC4A1 gene
Band 3 Coimbra
Waldner blood group expression
Autosomal recessive distal renal tubular acidosis with hemolytic anemia

SLC4A11 gene
Corneal endothelial dystrophy-2
Fuchs endothelial corneal dystrophy-4

SMAD4 gene
Myhre syndrome
Juvenile polyposis syndrome

SOS1 gene
Gingival fibromatosis-1
Form of Noonan syndrome

SOST gene
Craniodiaphyseal dysplasia, autosomal dominant
SclerosteosiS
Van Buchem disease

STAT1 gene
Mycobacterial and viral infections, susceptibility to, autosomal recessive
Familial chronic mucocutaneous candidiasis-7

SYCP3 gene
Spermatogenic failure 4
Recurrent pregnancy loss 4

TGFBR2 gene
Loeys-Dietz syndrome type 2B
Hereditary nonpolyposis colorectal cancer-6

TITIN GENE
Autosomal dominant dilated cardiomyopathy-1G
Limb-girdle muscular dystrophy type 2J
Tardive tibial muscular dystrophy

TMEM216 gene
Meckel syndrome type 2
Joubert syndrome-2

TNFRSF13B gene
Immunoglobulin A (IgA) deficiency-2
Common variable immunodeficiency-2

TREX1 gene
Aicardi-Goutieres syndrome-1 (can also be caused by mutations in the SAMHD1, TREX1, or Ribonuclease H2 genes)
Chilblain lupus-1

TRPV4 gene
Brachyolmia type 3
Metatropic dysplasia
Parastremmatic dwarfism
Form of scapuloperoneal spinal muscular atrophy
Maroteaux type of spondyloepiphyseal dysplasia
Kozlowski type of spondylometaphyseal dysplasia
Congenital distal spinal muscular atrophy
Hereditary motor and sensory neuropathy type IIC

TTR gene
Form of hereditary amyloidosis
Euthyroidal hyperthyroxinemia

TULP1 gene
Retinitis pigmentosa-14
Leber congenital amaurosis-15

VHL gene
Von Hippel-Lindau syndrome
Familial erythrocytosis-2

VSX1 gene
Posterior polymorphous corneal dystrophy-1
Craniofacial anomalies and anterior segment dysgenesis syndrome

WAS gene
Wiskott-Aldrich syndrome
X-linked thrombocytopenia
X-linked neutropenia

WDR35 gene
Cranioectodermal dysplasia-2
Short rib-polydactyly syndrome type V

WNK1 gene
Hereditary sensory and autonomic neuropathy type IIA
Form of pseudohypoaldosteronism type II

- Jules Berman

key words: rare diseases, allelic heterogeneity, allelic to, polymorphism, gene variation, genetic heterogeneity, genetics, genetics of disease, jules j berman

List of inherited syndromes associated with neoplasms

I've been trying to assemble a list of inherited conditions that carry an heightened risk of developing one or more neoplasms. The following are syndromes collected from OMIM (Online Mendelian Inheritance in Man) and each item is preceded by the OMIM identifier number. If anyone thinks that any of these items should be omitted or knows of additional items that should be added, please post them as a comment to this blog.

Familial syndromes associated with neoplastic development.

-1010000 Acoustic schwannomas bilateral

-1026600 Adamantinoma of long bones

-1027000 Severe combined immunodeficiency due to ada deficiency

-1035800 Albright hereditary osteodystrophy

-1056000 Anemia with multinucleated erythroblasts erythroreticulosis hereditary benign included

-1060700 Angioma hereditary neurocutaneous spinal arterial venous malformations with cutaneous hemangiomas included

-1062000 Aniridia

-1064000 Ankylosing vertebral hyperostosis with tylosis diffuse idiopathic skeletal hyperostosis included

-1074000 Serpina1 alpha-1-antitrypsin deficiency autosomal recessive included

-1093500 Gastroesophageal reflux pediatric adenocarcinoma of esophagus included

-1093900 Basal cell carcinomas with milia and coarse sparse hair

-1094000 Basal cell nevus syndrome

-1122000 Blue rubber bleb nevus

-1122500 Diaphyseal medullary stenosis with malignant fibrous histiocytoma

-1137050 Brca1 breast cancer type 1 included

-1139700 Burkitt lymphoma

-1140300 Cafe-au-lait spots multiple

-1144000 Lynch cancer family syndrome ii

-1153100 Carotid body tumors and multiple extraadrenal pheochromocytomas

-1168600 Cerebral capillary malformations cerebral cavernous malformations 1 included

-1175500 Sotos syndrome

-1182000 Charcot-marie-tooth neuropathy type 1b

-1183500 Chemodectoma intraabdominal with cutaneous angiolipomas

-1184500 Alagille-watson syndrome

-1188650 Choroidal osteoma bilateral

-1204350 Colorectal cancer hereditary nonpolyposis type 1

-1240300 Debrisoquine 4-hydroxylase codeine ultrarapid metabolism of included

-1240800 Aldosterone deficiency due to deficiency of 18-hydroxysteroid dehydrogenase included

-1242000 Keratosis follicularis (darier disease)

-1263370 Dna damage-inducible transcript 3 (gadd153 myxoid liposarcoma and chop/fus fusion gene included)

-1306500 Wiedemann-beckwith syndrome

-1311000 Multiple endocrine neoplasia type i

-1314400 Myeloproliferative disorder chronic with eosinophilia

-1314450 Ependymoma familial

-1326000 Pilomatrixoma

-1327000 Cylindromatosis familial

-1328100 Diphenylhydantoin defect lymphoproliferative disorders susceptibility to included

-1331000 Polycythemia familial

-1331800 Erythroleukemia familial

-1334500 Ews gene neuroepithelioma peripheral included

-1335100 Xeroderma pigmentosum complementation group b

-1337000 Exostoses multiple type i

-1351500 Birt-hogg-dube syndrome fibrofolliculomas with trichodiscomas and acrochordons

-1353000 Fibromatosis gingival hereditary

-1373570 Genitourinary dysplasia component of wagr syndrome

-1373600 Genochondromatosis

-1375500 Giant pigmented hairy nevus

-1375750 Gigantiform cementoma familial

-1378000 Glioma of brain familial glioblastoma multiforme included

-1388000 Goiter nontoxic with intrathyroidal calcification

-1410000 Hemangioma-thrombocytopenia syndrome kasabach-merritt syndrome

-1429810 Homeobox d4 hoxd4 acute lymphoblastic susceptibility to included

-1447000 Renal carcinoma familial associated 1 included

-1465100 Pallister-hall syndrome hypothalamic hamartoblastoma hypopituitarism imperforate anus and postaxial polydactyly

-1480000 Kaposi sarcoma

-1485000 Tylosis with esophageal cancer

-1490000 Klippel-trenaunay-weber syndrome angioosteohypertrophy syndrome

-1506990 Leiomyoma uterine

-1508000 Leiomyoma hereditary multiple of skin

-1516230 Li-fraumeni syndrome 1

-1534800 Bannayan-zonana syndrome macrocephaly pseudopapilledema and multiple hemangiomata bannayan-riley-ruvalcaba syndrome included

-1535500 5q- syndrome macrocytic anemia refractory due to 5q deletion

-1552400 Thyroid carcinoma familial medullary

-1556000 Dysplastic nevus syndrome hereditary b-k mole syndrome

-1583200 Muir-torre syndrome cutaneous sebaceous neoplasms and keratoacanthomas multiple with gastrointestinal and other carcinomas

-1583500 Cowden syndrome multiple hamartoma syndrome lhermitte-duclos disease included

-1595500 Myelocerebellar disorder

-1595550 Myeloid/lymphoid or mixed lineage leukemia trithorax drosophila homolog of mll/fbp17 fusion gene included

-1609800 Carney myxoma-endocrine complex carney syndrome

-1615500 Nasopharyngeal carcinoma

-1620910 Neurilemmomatosis congenital cutaneous

-1622000 Neurofibromatosis type i

-1622200 Nf3b

-1622400 Neurofibromatosis-pheochromocytoma-duodenal carcinoid syndrome

-1623000 Neuromata mucosal with endocrine tumors

-1630000 Nevi flammei familial multiple

-1632000 Linear sebaceous nevus syndrome

-1643300 Odontoma-dysphagia syndrome

-1660000 Osteochondromatosis

-1669500 Ovarian teratoma

-1680000 Paragangliomas familial 1

-1695450 Pelvic lipomatosis with crossed renal ectopia

-1714000 Multiple endocrine neoplasia type ii pheochromocytoma and amyloid-producing medullary thyroid carcinoma

-1714200 Pheochromocytoma--islet cell tumor syndrome

-1748000 Albright syndrome polyostotic fibrous dysplasia

-1750500 Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome

-1751000 Adenomatous polyposis of the colon apc

-1752000 Peutz-jeghers syndrome

-1764500 Sacral agenesis hereditary with presacral mass anterior meningocele and/or teratoma and anorectal malformation included

-1802000 Retinoblastoma

-1802950 Rhabdomyosarcoma embryonal 2

-1845000 Steatocystoma multiplex

-1866000 Syringomas multiple

-1873000 Telangiectasia hereditary hemorrhagic of rendu osler and weber

-1884000 Digeorge syndrome

-1884700 Thyroid carcinoma follicular

-1885500 Familial nonmedullary thyroid cancer

-1903450 Trichoepitheliomas multiple desmoplastic

-1906850 Leukemia megakaryoblastic of down syndrome

-1911000 Tuberous sclerosis

-1933000 Von hippel-lindau syndrome
-1940700 Wilms tumor 1

-1940800 Denys-drash syndrome nephropathy wilms tumor and genital anomalies

-1944000 Xeroderma pigmentosum autosomal dominant mild

-2019100 Adrenal hyperplasia congenital due to 21-hydroxylase deficiency

-2065500 Angiolipomatosis familial

-2089000 Ataxia-telangiectasia

-2109000 Bloom syndrome

-2119800 Lung cancer alveolar cell carcinoma included

-2276500 Fanconi anemia

-2285500 Fibromatosis congenital generalized

-2311000 Hemochromatosis neonatal

-2352000 Hemochromatosis

-2464000 Histiocytosis x acute disseminated

-2464700 Leukemia acute myelocytic with polyposis coli and colon cancer

-2544500 Myelofibrosis familial

-2547000 Myeloproliferative disease autosomal recessive

-2567000 Neuroblastoma

-2595000 Osteogenic sarcoma

-2595500 Osteoid osteoma

-2605000 Choroid plexus papilloma

-2633000 Polycythemia vera

-2670000 Nephroblastomatosis fetal ascites macrosomia and wilms tumor

-2677000 Hemophagocytic reticulosis familial

-2699500 Sideroblastic anemia autosomal

-2731200 Teratoma pineal

-2733000 Testicular tumors teratoma testicular included

-2763000 Turcot syndrome malignant tumors of the central nervous system associated with familial polyposis of the colon

-2787000 Xeroderma pigmentosum i

-3001470 Prostate cancer hereditary x-linked

-3018450 Follicular atrophoderma and basal cell carcinomas

-3053500 Epidermodysplasia verruciformis x-linked

-3082400 Lymphoproliferative disease x-linked

-3083000 Incontinentia pigmenti familial male-lethal type

-3089400 Leiomyomatosis esophageal and vulval with nephropathy

-3128200 Sarcoma synovial x-chromosome-related 1

-3128700 Dysplasia gigantism syndrome x-linked

-6000480 Breast cancer 11-22 translocation associated

-6000800 Myelocytic leukemia-like syndrome familial chronic

-6001390 Subependymoma

-6001850 Brca2 breast cancer type 2 included

-6001950 Venous malformations multiple cutaneous and mucosal

-6002580 Mismatch repair gene pmsl1 colorectal cancer hereditary nonpolyposis type 3 included

-6003760 Osler-rendu-weber syndrome 2

-6005420 Chondrosarcoma myxoid extraskeletal fused to ews

-6006780 Gtbp colorectal cancer hereditary nonpolyposis type 5 included

-6012230 Nid2

-6012280 Polyposis syndrome mixed hereditary

-6013210 Noonan-neurofibromatosis syndrome

-6013470 Myelodysplasia immunodeficiency facial dysmorphism short stature and psychomotor delay

-6013590 Sebaceous nevus syndrome and hemimegalencephaly

-6013630 Familial wilms tumor 1

-6013990 Platelet disorder familial with associated myeloid malignancy

-6015180 Prostate cancer hereditary 1

-6015830 Wilms tumor 5

-6016060 Trichoepithelioma multiple familial

-6016500 Glomus tumors familial 2

-6018030 Pallister-killian syndrome

-6018590 Canale-smith syndrome autoimmune lymphoproliferative syndrome type i autosomal dominant autoimmune lymphoproliferative syndrome type ia included

-6020890 Hemangioma capillary infantile

-6024500 Severe combined immunodeficiency with sensitivity to ionizing radiation

-6025960 Pancreatic lymphoma familial

-6033720 Thyroid carcinoma with thyrotoxicosis included

-6034390 Expansile bone lesions

-6035540 Reticuloendotheliosis familial with eosinophilia

-6036410 Neuroendocrine carcinoma of salivary glands sensorineural hearing loss and enamel hypoplasia

-6036560 Exostosis dupuytren subungual

-6036690 Eccrine syringofibroadenomatosis with eyelid abnormalities

-6036700 Blue nevi familial multiple

-6036880 Prostate cancer/brain cancer susceptibility

-6037370 Ovarian germ cell cancer

-6037440 Papillary thyroid microcarcinoma

-6042870 Carney triad

-6042870 Gastric leiomyosarcoma pulmonary chondroma and extraadrenal paraganglioma

-6043700 Epithelial ovarian cancer

-6043730 Checkpoint kinase 2 s. pombe homolog of breast and colorectal cancer susceptibility to included

-6044420 Nonpapillary renal carcinoma 1

-6044510 Basal cell carcinoma with follicular differentiation

-6048560 Langerhans cell histiocytosis

-6049190 Becker nevus syndrome

-6050270 Lymphoma non-hodgkin familial

-6050410 Spiegler-brooke syndrome

-6050740 Renal cell carcinoma papillary

-6050750 Renal cell carcinoma papillary 3

-6052330 Autoimmune lymphoproliferative disease without fas mutations

-6052440 Carney myxoma-endocrine complex type ii

-6052880 Primordial germ cell tumor susceptibility locus 1

-6053650 Breast cancer 3 brca3

-6053730 Paragangliomas 3

-6053730 Glomus tumors familial 3

-6054620 Basal cell carcinoma multiple

-6056420 Thyroid carcinoma papillary with papillary renal neoplasia

-6058270 Basaloid follicular hamartoma syndrome generalized autosomal dominant

-6058390 Leiomyomatosis and renal cell cancer hereditary

-6059820 Familial wilms tumor 2

-6061790 Aneurysmal bone cysts

-6061900 Meningioma radiation-induced

-6062400 Thyroid carcinoma nonmedullary 1

-6062430 Alveolar soft-part sarcoma

-6064450 Persistent polyclonal b-cell lymphocytosis

-6065190 Phace association

-6066600 Melanoma uveal susceptibility to 1

-6066900 Lymphangioleiomyomatosis

-6066900 Lymphangiomyomatosis lymphangioleiomyomatosis somatic included

-6067190 Familial atypical multiple mole melanoma-pancreatic carcinoma syndrome

-6067640 Gastrointestinal stromal tumor gist

-6068640 Paraganglioma and gastric stromal sarcoma

-6068930 Hemangioma intraosseous

-6071740 Meningioma familial meningioma caused by somatic mutation included

-6072480 Glioma familial 1

-6072780 Osteofibrous dysplasia

-6074640 Thyroid carcinoma hurthle cell

-6076850 Hypereosinophilic syndrome idiopathic

-6077850 Juvenile myelomonocytic leukemia

-6078590 Tufted angioma

-6078930 Ovarian cancer epithelial susceptibility to

-6079070 Dermatofibrosarcoma protuberans

-6080350 Melanoma cutaneous malignant 4

-6082320 Leukemia chronic myeloid

-6082660 Parathyroid carcinoma

-6083540 Capillary malformation-arteriovenous malformation

-6084560 Colorectal adenomatous polyposis autosomal recessive

-6086150 Oligodontia-colorectal cancer syndrome

-6086230 Neuroectodermal tumors supratentorial primitive with cafe-au-lait spots

-6086560 Prostate cancer hereditary 20

-6086580 Prostate cancer hereditary 7

-6088120 Colorectal cancer susceptibility to on chromosome 9

-6088370 Carney complex variant

-6089350 Lung cancer 1

-6090480 Melanoma cutaneous malignant 3

-6092990 Prostate cancer hereditary 3

-6093100 Colorectal cancer hereditary nonpolyposis type 2

-6093220 Rhabdoid tumor

-6093630 Colloid cysts of third ventricle

-Jules J. Berman

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In June, 2014, my book, entitled Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases was published by Elsevier. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

I urge you to read more about my book. There's a generous preview of the book at the Google Books site.

- Jules J. Berman, Ph.D., M.D. tags: common disease, orphan disease, orphan drugs, genetics of disease, disease genetics, rules of disease biology, rare disease, pathology, cancer, genetics, neoplasia, neoplasms, tumor, tumour