PhenomeCentral: An Integrated Portal for Sharing Patient Phenotype and Genotype Data for Rare Genetic Disorders. M. Brudno1, M. Girdea1, O. J. Buske1, S. Dumitriu1, H. Trang1, T. Hartley2, D. Smedley3, S. Kohler4, P. N. Robinson4, T. E. Dudding5, H. Lochmuller6, C. F. Boerkoel7, W. A. Gahl7, K. Boycott2, Canadian CARE for RARE, NIH Undiagnosed Diseases Program, RD-Connect, Care for Rare Australia 1) Centre for Computational Medicne, Hospital for Sick Children & University of Toronto, Toronto, ON, Canada; 2) Children's Hospital of Eastern Ontario, Ottawa, ON Canada; 3) Sanger Institute, Hinxton, UK; 4) Institute for Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Germany; 5) Hunter Genetics and University of Newcastle, Newcastle, NSW, Australia; 6) Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; 7) National Institutes of Health Undiagnosed Diseases Program, NIH, Bethesda USA.
The availability of low-cost genome sequencing has allowed for the identification of the molecular cause of hundreds of rare genetic disorders. Solved disorders, however, represent only the tip of the iceberg. Because the discovery of disease-causing variants typically requires confirmation of the mutation or gene in multiple unrelated individuals, a larger number of genetic disorders remain unsolved due to difficulty identifying second families. As many groups are now tackling these remaining undiagnosed disorders, which may be present in only a handful of individuals seen at different hospitals and sequenced by different centers, there is a pressing need for tools enabling global collaboration.
To help clinicians and rare disorder scientists identify additional families with a specific rare disease through sharing of genetic and phenotypic data, we have developed PhenomeCentral (http://phenomecentral.org). Each patient record within PhenomeCentral consists of a thorough phenotypic description capturing observed abnormalities and relevant absent manifestations expressed using Human Phenotype Ontology terms, as well as the observed genetic variants, specified either as a whole exome/genome or a list of candidate genes. New patients can be added either using the PhenoTips User Interface, built into PhenomeCentral, or uploaded in bulk. For a given patient record the contributor is shown information about other phenotypically similar patients, together with potential genetic causes, prioritized by the Exomiser algorithm. The phenotypic and genetic features are presented without revealing additional patient information or identifying the contributors, while enabling direct communication for any subsequent data sharing. PhenomeCentral currently incorporates phenotype data for >450 patients with rare genetic disorders lacking molecular diagnosis, including 260 with available whole exome/genome data. PhenomeCentral has been used to identify the likely causative mutation in the EFTUD2 gene in two patients with atypical presentations, as well as to generate leads by identifying novel phenotypic clusters with mutations in several genes. Participants in PhenomeCentral include the Canadian CARE for RARE project, the NIH Undiagnosed Diseases Program, RD-Connect, and Care for Rare Australia. Membership is open to all clinicians and rare disorder scientists affiliated with academic or not-for-profit research centers.