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Monogenic hearing loss v4.6 ATP2B2 Eleanor Williams changed review comment from: Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on HI, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.; to: Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on Hearing impairment, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.
Monogenic hearing loss v1.122 ATP2B2 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. PMID 30535804 reports 5 independent cases of autosomal dominant hearing impairment in individuals with truncating or splice site variants. Rare variants in CDH23 were considered unlikely to be causative. However, they cannot exclude a modifying effect of the CDH23 variants on HI, therefore rating amber until further cases on monogenic hearing loss with ATP2B2 are reported.
Monogenic hearing loss v1.117 ATP2B2 Eleanor Williams edited their review of gene: ATP2B2: Added comment: PMID: 30535804 - Smits et al 2019 - report 5 independant cases. Whole exome sequencing in hearing impaired index cases of Dutch and Polish origins revealed five novel heterozygous (predicted to be) loss-of-function variants of ATP2B2. Two variants, c.1963G>T (p.Glu655*) and c.955delG (p.Ala319fs), occurred de novo. Three variants c.397+1G>A (p.?), c.1998C>A (p.Cys666*), and c.2329C>T (p.Arg777*), were identified in families with an autosomal dominant inheritance pattern of hearing impairment. In most cases HI was early onset, but in one individual hearing loss was reported around 55 years. Whole exome sequence (WES) data were analyzed for variants in a panel of 142 genes known to be associated with nonsyndromic hearing impairment (HI) and relatively common syndromic forms of HI. All variants affect exons, or their splice sites, that encode the ortholog of the rat PMCA2 w/a isoform. This isoform is highly abundant in stereocilia of outer hair cells (OHC) and to a lesser extent at the apical surface of inner hair cells of rats.

Although rare CDH23 variants cooccurred with ATP2B2 variants in all five index cases, they state their findings indicate that mono-allelic loss-of-function variants of ATP2B2 are the underlying cause of HI. However, variants in deep intronic regions or promoter regions were not addressed and can, therefore, not be excluded. CNVs of CDH23 can be excluded for the index cases only. They state they cannot exclude a modifying effect of the CDH23 variants on HI in the affected subjects in their study.; Changed publications: 30535804
Monogenic hearing loss v1.43 CDH23 Ellen McDonagh commented on gene: CDH23: New review confirms gene status and mode of inheritance; no changes required.
Monogenic hearing loss CDH23 Lampros Mavrogiannis reviewed CDH23