One of the key messages of the book is that common diseases are complex, with multiple causes, lots of associated gene variations, many different aberrant pathways, and affecting heterogeneous populations (e.g., subsets of people who seem to have clinically distinctive forms of the same disease, or subsets of people who respond quite differently to the same treatment).
Contrariwise, rare diseases are usually simple: one cause, one responsible gene, one aberrant pathway, often strikingly uniform clinical features.
In Chapter 12, I build the case that particular subsets of the common diseases can often be accounted for by rare diseases. Rare diseases that account for subsets of common diseases typically have a monogenic cause, and occur at a young age (as we see in most other rare diseases). An example would be midline lung cancer of the young, a rare subset of lung cancer caused by a mutation in the NUT gene.
Here is an excerpt from Chapter 12, in which rare diseases accounting for subsets of some of the common diseases, are listed:
- MODY (maturity onset diabetes of the young), also known as monogenic diabetes, refers to any of several hereditary forms of the disease. Despite its name, MODY has a childhood onset, like most other rare diseases. The “maturity onset” in its name refers to its common disease counterpart.
- Fragile X syndrome (FXS), also known as Martin–Bell syndrome, is a monogenic cause of autism.
- McKusick–Kaufman syndrome and Bardet–Biedl syndrome-6 are both diseases that include a monogenic form that causes obesity.
- Monogenic emphysema due to alpha-1-antitrypsin deficiency .
- Monogenic gallstone disease due to a mutation in the ABCB4 gene.
- Monogenic cardiomyopathy due to a mutation in the ABCC9 gene.
- Monogenic cardiac arrhythmia due to monogenic mutations in ion channel genes (see Section 5.3).
- Monogenic cause of migraine in familial hemiplegic migraine type 2 and familial basilar migraine due to mutations in the gene encoding the alpha-2 subunit of the sodium/potassium pump.
- Monogenic osteoarthritis, as a component of familial osteochondritis dissecans, due to mutation in the ACAN gene.
- Familial Alzheimer disease type 1 due to a mutation in the gene encoding the amyloid precursor protein.
- Monogenic, Mendelian forms of hypertension associated with proteins involved, in one way or another, with the transport of electrolytes in the renal tubules (see Section 5.4 for detailed discussion). Changes in electrolyte transport result in increased retention of sodium and to an increased volume of body fluid [33–35].
- Autoinflammatory syndromes with monogenic subtypes, including familial Mediterranean fever caused by a mutation in the MEFV gene encoding pyrin ."
These, and many other examples discussed in my book, indicate that if the common diseases are puzzles, then the rare diseases are the pieces of the puzzle.
I urge you to read more about this book. There's a good preview of the book at the Google Books site. If you like the book, please request your librarian to purchase a copy of this book for your library or reading room.
- Jules J. Berman, Ph.D., M.D.