The DIAPH1 gene has been associated with autosomal dominant hearing loss and thrombocytopenia using the ClinGen Clinical Validity Framework as of 2/24/17. Families with segregations have been reported in the original paper in 1997 (Lynch et al.) and in three additional publications (27808407, 27068579, 26912466). The original paper did not report thrombocytopenia, though it can be subclinical and cannot be excluded from this family. All variants in these families have been LOF/truncating variants in exon 27. The mechanism for disease is not clear, but Ueyama 2016 provides evidence LOF is not a mechanism for hearing loss (27707755). Of note, LOF variants in other exons of this gene have been implicated in autosomal recessive microcephaly and seizures. This disease is not covered by the scope of this curation. In summary, DIAPH1 is definitively associated with autosomal dominant hearing loss and thrombocytopenia. 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 Working Group on 1/5/18.
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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