HGF was first reported in relation to autosomal recessive nonsyndromic hearing loss (AR NSHL) in 2009 (Schultz et al., 19576567). At least three unique variants (silent, deep intronic deletions) that have been reported in 3 probands in one publication are included in this curation (PMID: 19576567). One of the deep intronic deletions is a founder variant in Pakistan and is present in at least 36 families with hearing loss (PMID: 19576567). Variants in this gene also segregated with disease in at least 41 additional individuals in 22 families (PMID: 19576567). The mechanism for disease is likely loss of function. This gene-disease relationship is supported by expression and biochemical function studies, along with at least four mouse models, one of which recapitulates the deafness phenotype with the same 10 bp deletion of Hgf in the intron in humans (27488639, 19576567, 32152201). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was originally evaluated by the ClinGen Hearing Loss GCEP on 1/16/2018 as per SOP v5. It was reevaluated on 5/3/2024 using SOP v10. No new evidence has been reviewed or added. As a result of this reevaluation, the classification did not change.
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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