The future is now for rare genetic diseases
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* Alex MacKenzie
* Kym M. Boycott

We agree with the cautionary note sounded by Roger Collier with respect to the hype surrounding genomic medicine.1 In most cases a careful medical and family history combined with a thorough 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.

These individually rare but collectively frequent disorders affect an estimated 1 in 12 Canadians.2 Although 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, affecting thousands of families.3

One estimate is that within a decade the clinical and biological impact of mutations in a third of all human genes shall be known,4 truly a remarkable wealth of pathogenic knowledge that will profoundly affect our understanding of human biology at a molecular level. Moreover, given the shared phenotypic overlap with more common disorders, insight into these latter conditions might also be forthcoming.

Clinical impact is equally important. Patients might no longer be consigned to costly and often fruitless diagnostic odysseys while confronting an unknown future. Disease gene identification could bring diagnostic clarity (obviating extensive and expensive testing), suggest chance of recurrence within the family and define future clinical course and optimal medical management. Translational research for “common” rare diseases, such as Duchenne muscular dystrophy, spinal muscular atrophy and cystic fibrosis, has led to some thought regarding the generalized formulation to therapeutic approaches for the thousands of the other rare conditions.5 Although the promise of genomic medicine lies ahead for complex disorders, the future is now for rare genetic diseases.

## References

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2.  Fundraising tool kit. Toronto (ON): Canadian Organization for Rare Disorders. Available: [www.raredisorders.ca/documents/CORDFundraisingToolKit.pdf](http://www.raredisorders.ca/documents/CORDFundraisingToolKit.pdf) (accessed 2012 June 21).
    
    

3.  Finding of Rare Disease Genes Project. Ottawa (ON): Canadian Pediatric Genetic Disorders Sequencing Consortium; 2010. Available: [www.cpgdsconsortium.com/](http://www.cpgdsconsortium.com/) (accessed 2012 June 21).
    
    

4.  Samuels M. Saturation of the human phenome. Current Genomics 2010;11:482–99.
    
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5.  Beaulieu CL, Samuels ME, Ekins S, et al. A generalizable pre-clinical research approach for orphan disease therapy. Orphanet J Rare Dis 2012;7:39.
    
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