FGF3 was first reported in relation to autosomal recessive deafness with labyrinthine aplasia, microtia, and microdontiain (LAMM) syndrome in 2007 (Tekin et al., PMID 17236138). At least 11 variants (e.g. missense, nonsense, frameshift) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data, experimental data. Variants in this gene have been reported in at least 12 probands in 6 publications (PMIDs 21480479, 21306635, 18435799, 17236138, 21306635, 18701883). Variants in this gene segregated with disease in at least 41 additional family members. More evidence is available in the literature, but the maximum score for genetic evidence and experimental evidence (12 pts.) has been reached. The mechanism for disease appears to be homozygous loss of function based on the variants observed in patients. This gene-disease association is supported by animal models, expression studies and in vitro functional assays (PMIDs 8223243, 26995070, 29902227, 30504125). In summary, FGF3 is definitively associated with autosomal recessive deafness with LAMM syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Hearing Loss Expert Panel on 5/21/2019 (SOP Version 6).
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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