GeneMatcher

As of December 2019^[update], the site contained 11,855 genes from 7,724 submitters from 88 countries, and 6,609 matches had been made.^[2] As of July 2015^[update], roughly 14% of the genes were related to animal models, and the BHCMG itself had submitted at least 180 of the genes and generated 69 matches, 16 of which were also a phenotype match. Three of those phenotype–gene matches, involving SPATA5, HNRNPK and TELO2, were sufficient for publication of new outlines of diseases in medical journals.^[1]

GeneMatcher is part of a collaboration between multiple gene-matching services called MatchmakerExchange,^[5] launched in October 2013. The other services part of the project include PhenomeCentral and DECIPHER.^[6]

American genetic testing company GeneDx has uploaded genes from its database with likely pathogenic variants, leading to dozens of matches.^[1]

GeneMatcher has helped geneticists to make several new discoveries, some examples of which include the following:

• In 2015, the service matched three practices with cases of an unknown multi-system syndrome likely caused by a mutation in HNRNPK. The cause was confirmed, and the syndrome was named Au–Kline syndrome, after Ping-Yee Billie Au and Antonie D. Kline, two of the researchers involved.^[6][7] The syndrome was later shown in 2019 to be identical to Okamoto syndrome, described in 1997.^[8]
• In 2015, the service allowed researchers to link SPATA5 to an autosomal recessive syndrome of microcephaly, seizures and hearing loss. They used GeneMatcher to find 4 of 14 patients with the syndrome and mutations.^[9]
• In 2015, GeneMatcher helped researchers to link TELO2 to an autosomal recessive syndrome of microcephaly, ataxia, hearing loss, congenital heart defects and other features. The service allowed them to find the fourth of four families with children with the condition and mutations. The syndrome was named You–Hoover-Fong syndrome, after researchers Jing You and Julie Hoover-Fong.^[10]
• In 2016, researchers in the Netherlands used GeneMatcher to identify 2 of 4 patients with a fatal autosomal recessive immunodeficiency condition called LICS syndrome, caused by mutations in NSMCE3.^[11][12]
• In 2017, it was discovered that mutations in KYNU or HAAO lead to an autosomal recessive syndrome of skeletal abnormalities, congenital heart defects, hypoplastic kidneys, hearing loss and other features. The researchers used GeneMatcher to identify the fourth of four families with children with the condition.^[13][14]
• In 2017, UK researchers identified mutations in ADCY3 as the cause of an autosomal recessive ciliary disorder causing obesity, anosmia and mild intellectual disability. GeneMatcher allowed them to find the fourth of four patients with the condition.^[15][16][17]
• In 2018, researchers were able to associate a mitochondrial complex I deficiency with a mutation in NDUFA6 using GeneMatcher. The service allowed them to locate 3 of 4 patients with the condition and mutation.^[18][19]
• In 2019, GeneMatcher allowed researchers to link DEGS1 to an autosomal recessive hypomyelinating leukodystrophy. They had found a homozygous mutation in the gene in one female patient, and the service helped them in finding 18 other patients with autosomal recessive mutations in the same gene with similar symptoms.^[20][21][22]
• In 2019, researchers were able to establish with the help of GeneMatcher that a mutation in BRSK1 leads to an autosomal dominant syndrome of intellectual disability and autism spectrum disorder. The service allowed them to find 5 of 9 patients with the condition and mutation. The nine patients were from cohorts totalling 3,429 individuals, which was considered a high prevalence for a rare disorder and led to surprise that the gene hadn't been linked to developmental delay before.^[23][24]