Format

Send to

Choose Destination
Am J Hum Genet. 2017 May 4;100(5):695-705. doi: 10.1016/j.ajhg.2017.04.003.

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

Author information

1
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada. Electronic address: kboycott@cheo.on.ca.
2
Orphanet, Institut National de la Santé et de la Recherche Médicale US14, 75014 Paris, France.
3
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
4
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
5
Department of Genetics, King Faisal Research Center, Riyadh 11211, Saudi Arabia; Saudi Human Genome Program, King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia.
6
Genetic Services of Western Australia, Perth, WA 6008, Australia.
7
Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
8
Department of Computer Science, University of Toronto, Toronto M5S 1A1, Canada.
9
Genomic Medicine Group, Galician Foundation of Genomic Medicine and University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
10
Departments of Human Genetics and Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
11
Centre of Genomics and Policy, Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, QC H3A 1A4, Canada.
12
Experimental Division, Sidra Medical and Research Center, PO Box 26999, Doha, Qatar; Genetics Unit, Dexeus Woman's Health, 08028 Barcelona, Spain.
13
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-4874, USA.
14
Centre Nacional d'Anàlisi Genòmica, Center for Genomic Regulation, Barcelona Institute of Science and Technology, Universitat Pompeu Fabra, 08028 Barcelona, Spain.
15
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21286, USA.
16
Michael Smith Laboratories, Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
17
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
18
Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-4874, USA.
19
University of South Florida Health Informatics Institute, Tampa, FL 33620, USA.
20
Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and University Hospital Motol, 150 06 Prague 5, Czech Republic.
21
Center for Human Genetics, University of Leuven, 3000 Leuven, Belgium.
22
Lysogene, 92 200 Neuilly-sur-Seine, France.
23
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
24
Institut für Medizinische Genetik und Humangenetik, Charité Universitätsmdizin Berlin, 13353 Berlin, Germany; Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
25
Centre for Genomic Sciences, University of Hong Kong, Hong Kong, China.
26
Department of Social Medicine and Public Health, Faculty of Public Health, Medical University of Plovdiv, Plovdiv 4002, Bulgaria.
27
National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome 299-00161, Italy.
28
WuXi AppTec, Waigaoqiao Free Trade Zone, Shanghai 200131, China; WuXi NextCODE, Cambridge, MA 02142, USA.
29
Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Maastricht University Medical Center, Department of Clinical Genetics, 6229 GT Maastricht, the Netherlands.
30
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA; Division of Genetic Medicine, Seattle Children's Hospital, Seattle, WA 98105, USA.
31
John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.

Abstract

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.

KEYWORDS:

IRDiRC; Matchmaker Exchange; disease modeling; gene discovery; genome sequencing; ontologies; rare diseases; solving the unsolved; transcriptome sequencing

PMID:
28475856
PMCID:
PMC5420351
DOI:
10.1016/j.ajhg.2017.04.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center