International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases.

TitleInternational Cooperation to Enable the Diagnosis of All Rare Genetic Diseases.
Publication TypeJournal Article
Year of Publication2017
AuthorsBoycott, KM, Rath, A, Chong, JX, Hartley, T, Alkuraya, FS, Baynam, G, Brookes, AJ, Brudno, M, Carracedo, A, Dunnen, JT den, Dyke, SOM, Estivill, X, Goldblatt, J, Gonthier, C, Groft, SC, Gut, I, Hamosh, A, Hieter, P, Höhn, S, Hurles, ME, Kaufmann, P, Knoppers, BM, Krischer, JP, Macek, M, Matthijs, G, Olry, A, Parker, S, Paschall, J, Philippakis, AA, Rehm, HL, Robinson, PN, Sham, P-C, Stefanov, R, Taruscio, D, Unni, D, Vanstone, MR, Zhang, F, Brunner, H, Bamshad, MJ, Lochmüller, H
JournalAm J Hum Genet
Date Published2017 May 04
KeywordsDatabases, Factual, Exome, Genome, Human, Humans, International Cooperation, Rare Diseases

Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their "diagnostic odyssey," improves disease management, and fosters genetic counseling with respect to recurrence risks while assuring reproductive choices. In a general clinical genetics setting, the current diagnostic rate is approximately 50%, but for those who do not receive a molecular diagnosis after the initial genetics evaluation, that rate is much lower. Diagnostic success for these more challenging affected individuals depends to a large extent on progress in the discovery of genes associated with, and mechanisms underlying, rare diseases. Thus, continued research is required for moving toward a more complete catalog of disease-related genes and variants. The International Rare Diseases Research Consortium (IRDiRC) was established in 2011 to bring together researchers and organizations invested in rare disease research to develop a means of achieving molecular diagnosis for all rare diseases. Here, we review the current and future bottlenecks to gene discovery and suggest strategies for enabling progress in this regard. Each successful discovery will define potential diagnostic, preventive, and therapeutic opportunities for the corresponding rare disease, enabling precision medicine for this patient population.

Alternate JournalAm. J. Hum. Genet.
PubMed ID28475856
PubMed Central IDPMC5420351
Grant ListUM1 HG008900 / HG / NHGRI NIH HHS / United States
U54 HG006493 / HG / NHGRI NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
/ / Wellcome Trust / United Kingdom
U41 HG006627 / HG / NHGRI NIH HHS / United States