De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment.

ABSTRACT: ATP2B2 encodes the PMCA2 Ca²⁺ pump that plays an important role in maintaining ion homeostasis in hair cells among others by extrusion of Ca²⁺ from the stereocilia to the endolymph. Several mouse models have been described for this gene; mice heterozygous for loss-of-function defects display a rapidly progressive high-frequency hearing impairment. Up to now ATP2B2 has only been reported as a modifier, or in a digenic mechanism with CDH23 for hearing impairment in humans. 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.Cys

SUBMITTER: Smits JJ 

PROVIDER: S-EPMC6514080 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature