GeneMatcher: A Matching Tool for Connecting Investigators with an Interest in the Same Gene

Abstract

Here, we describe an overview and update on GeneMatcher (http://www.genematcher.org), a freely accessible Web-based tool developed as part of the Baylor-Hopkins Center for Mendelian Genomics. We created GeneMatcher with the goal of identifying additional individuals with rare phenotypes who had variants in the same candidate disease gene. We also wanted to facilitate connections to basic scientists working on orthologous genes in model systems with the goal of connecting their work to human Mendelian phenotypes. Meeting these goals will enhance the identification of novel Mendelian genes. Launched in September, 2013, Gene-Matcher now has 2,178 candidate genes from 486 submitters spread across 38 countries entered in the database (June 1, 2015). GeneMatcher is also part of the Match-maker Exchange (http://matchmakerexchange.org/) with an Application Programing Interface enabling submitters to query other databases of genetic variants and phenotypes without having to create accounts and data entries in multiple systems.

Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome

“…52,53 A homozygous extended splice site mutation, c.322À10G>A, was identified in subjects 2a, 2b, 3a, and 3b of Puerto Rican ethnicity; these subjects were ascertained with assistance from the GeneMatcher tool. 54 This variant is predicted to abolish the acceptor splice site and create a new cryptic splice acceptor site within intron 1, causing abnormal gene splicing. The MRPS34 c.322À10G>A variant is reported in dbSNP (rs563189672), and two heterozygous individuals (both of Latino ethnicity) were reported in the gnomAD Browser (2 of 236,804 alleles examined, no homozygotes observed).…”

Loss-of-Function and Gain-of-Function Mutations in KCNQ5 Cause Intellectual Disability or Epileptic Encephalopathy

“…GeneMatcher postings, and subsequent communications, enabled independent discoveries to be corroborated. 10 Written informed consent for exome sequencing and approval by ethics review boards were obtained from Erasmus Medical Center (protocol MEC-2012387) for individual 1 and from the University of British Columbia (protocols H-15-00092, H-09-01228, and H-14-01531) for individuals 2 and 4. Individual 3 received sequencing through clinical care, and written informed consent was obtained for publication of medical history.…”

De Novo Mutations in YWHAG Cause Early-Onset Epilepsy

“…In an attempt to identify additional carriers of de novo variants in SLC1A2 and YWHAG, we queried biomedical literature on PubMed and three online resources: (1) GeneMatcher, 21 a freely accessible tool that connects clinicians and researchers with interests in the same gene; (2) DECIPHER, which contains exome sequencing data from nearly 4,300 families affected by developmental disorders; 22,23 [REVEL]). None have been reported in public databases (gnomAD Browser), and one mutation (YWHAG c.394C>T) is recurrent in three subjects (B, E, and F).…”