Hearing lossGene: ATP6V1B2
Comment on list classification: Sufficient cases with Deafness, congenital, with onychodystrophy to rate green. This gene should be reviewed at the next GMS update.
Created: 11 Sep 2020, 1:31 p.m. | Last Modified: 11 Sep 2020, 3:28 p.m.
Panel Version: 2.68
Adding gene at request of Alistair Pagnamenta (University of Oxford).
Associated with Deafness, congenital, with onychodystrophy, autosomal dominant #124480 (AD) and Zimmermann-Laband syndrome 2 #616455 (AD) in OMIM.
PMID: 32873933 Beauregard-Lacroix et al 2020 - identified the same truncating variant in ATP6V1B2 (NM_001693.4:c.1516C>T; p.Arg506*) in nine individuals from eight unrelated families with DOORS syndrome. All individuals presented with deafness as well as as onychodystrophy and abnormal fingers and/or toes. In addition, all families but one had developmental delay or intellectual disability and five individuals had epilepsy. Two additional familes with dominant deafness onychodystrophy (DDOD) syndrome also had the same variant in ATP6V1B2. Abstract only accessed.
PMID: 28396750 Menendez et al 2017 - report a Guatemalan famliy with one child with deafness–onychodystrophy. The proband was found to be heterozygous for c.1516C>T [p.(Arg506*)] in ATP6V1B2. Neither parents or sisters had this variant.
PMID: 24913193 Yuan et al 2014 - report 3 Chinese families with severe congenital sensorineural hearing loss, absence of nails and aplasia of the middle phalanx in the fifth fingers, but no inner ear malformation or intellectual disability. Using exome sequencing an identical heterozygous de novo c.1516 C>T (p.Arg506X) mutation in ATP6V1B2 was verified in two probands. In the third family the same variant was found by Sanger sequencing. A cochlea-specific Atp6v1b2-knockdown mouse model demonstrates that Atp6v1b2 deficiency leads to severe sensorineural hearing loss.
Created: 11 Sep 2020, 1:29 p.m. | Last Modified: 11 Sep 2020, 3:27 p.m.
Panel Version: 2.68
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ATP6V1B2 were changed from to Deafness, congenital, with onychodystrophy, autosomal dominant, 124480; Zimmermann-Laband syndrome 2, 616455
Publications for gene: ATP6V1B2 were set to
Tag for-review tag was added to gene: ATP6V1B2.
Gene: atp6v1b2 has been classified as Amber List (Moderate Evidence).
Gene: atp6v1b2 has been classified as Red List (Low Evidence).
gene: ATP6V1B2 was added gene: ATP6V1B2 was added to Hearing loss. Sources: Expert Review,Literature Mode of inheritance for gene: ATP6V1B2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown