Popping the genetics bubble

We agree with the cautionary note recently sounded by Roger Collier with respect to the hype surrounding genomic medicine; in most cases a careful medical and family history combined with a good physical examination has as much, and very likely more, clinical prognostic power than does a complete genome sequence. There is, however, one area that we believe even now is delivering on the promise of modern genomics; the oft neglected realm of orphan (rare) disease. It is currently estimated that one in 12 Canadian families is impacted by these individually rare but collectively frequent disorders (www.raredisorders.ca). While the genetic etiology of the significant majority of rare disorders is still unknown, the advent of next-generation DNA sequencing is resulting in the identification of rare and ultra rare disease genes at an ever increasing rate. This accelerating pace of discovery is best exemplified by the internationally leading Canadian FORGE (Finding of Rare Disease Genes) project, which in its first year alone had identified genes for over 50 rare disorders, impacting thousands of families (www.cpgdsconsortium.com).

It is estimated that within the decade the clinical and biological impact of mutations in a full third of all human genes shall be known, truly a remarkable wealth of pathogenic knowledge which will profoundly affect our understanding of human biology at a molecular level. Moreover, it is a certainty given the shared phenotypic overlap with more common disorders that insight into these latter conditions will also be forthcoming.

Equally important is the clinical impact. Heretofore, those affected with such frequently serious conditions were consigned to costly and often fruitless diagnostic odysseys while confronting an unknown future. Increasingly, disease gene identification brings diagnostic clarity, obviating extensive and expensive testing, and informing chance of recurrence within the family as well as future clinical course and optimal medical management. Although definitive treatments lie well in the future for most rare disorders, taking lessons from translational research for the 'common' rare diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, and cystic fibrosis, some thought to the generalized formulation to therapeutic approaches for the hundreds and thousands of the other rare conditions is underway.1 So while the promise of genomic medicine lies ahead for complex disorders, the future is now for rare genetic diseases.

1.Beaulieu CL, Samuels ME, Ekins S, et al. A generalizable pre- clinical research approach for orphan disease therapy. Orphanet Journal of Rare Diseases 2012; 7:39.

Conflict of Interest:

None declared