The relationship between GRXCR1 and autosomal recessive nonsyndromic hearing loss was evaluated using the ClinGen Clinical Validity Framework as of 10/31/2017. Variants in GRXCR1 were first reported in humans with this disease as early as 2010 (Schraders et al.). At least 7 missense, nonsense, and frameshift variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 6 probands in 5 publications (20137778, 25802247, 26226137, 26445815, 26969326). Variants in this gene segregated with disease in 6 additional family members. This gene-disease association is supported by relevant expression and protein interaction studies, as well as multiple mouse models published by Odeh et al. 2010. In summary, GRXCR1 is definitively associated with autosomal recessive nonsyndromic hearing loss. This classification was approved by the ClinGen Hearing Loss Working Group on 4/24/2018.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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