Monogenic hearing loss
Gene: PPIP5K2
Comment on list classification: Promoting this gene from grey to amber. 2 cases (but with same variant, likely founder effect) plus mouse model replicating disease.Created: 4 Nov 2020, 3:28 p.m. | Last Modified: 4 Nov 2020, 3:28 p.m.
Panel Version: 2.106
Associated with Deafness, autosomal recessive 100 #618422 (AR) in OMIM.
PMID: 29590114 - Yousaf et al 2018 - report 2 large apparently unrelated consanguineous Pakistani families in which a variant in PPIP5K2 (c.2510G>A, p.Arg837His) was found to segregate with DFNB100-associated hearing loss. Subsequent SNP analysis in the flanking region in affected individuals suggest the haplotype is consistent with a founder effect for the identified variant. Expression studies found that PPIP5K2 is expressed in mouse cochlear and vestibular sensory hair cells, supporting cells and spiral ganglion neurons. Mice with a homozygous deletion of the Ppip5k2 phosphatase domain show degeneration of cochlear outer hair cells and elevated hearing thresholds.
A PubMed search does not find any further cases.Created: 4 Nov 2020, 3:24 p.m. | Last Modified: 4 Nov 2020, 3:24 p.m.
Panel Version: 2.104
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Deafness, autosomal recessive 100, 618422; deafness, autosomal recessive 100 MONDO:0032740
Publications
Two apparently unrelated families with multiple affecteds segregating a homozygous missense variant; mouse model.
Sources: Expert listCreated: 2 Jan 2020, 5:15 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Deafness, autosomal recessive 100, MIM#618422
Publications
Gene: ppip5k2 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: PPIP5K2 were changed from Deafness, autosomal recessive 100, MIM#618422 to Deafness, autosomal recessive 100, MIM#618422; deafness, autosomal recessive 100 MONDO:0032740
gene: PPIP5K2 was added gene: PPIP5K2 was added to Hearing loss. Sources: Expert list Mode of inheritance for gene: PPIP5K2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPIP5K2 were set to 29590114 Phenotypes for gene: PPIP5K2 were set to Deafness, autosomal recessive 100, MIM#618422 Review for gene: PPIP5K2 was set to AMBER