z-logo
Premium
Targeted and Genomewide NGS Data Disqualify Mutations in MYO 1 A , the “ DFNA 48 Gene”, as a Cause of Deafness
Author(s) -
Eisenberger Tobias,
Di Donato Nataliya,
Baig Shahid M.,
Neuhaus Christine,
Beyer Anke,
Decker Eva,
Mürbe Dirk,
Decker Christian,
Bergmann Carsten,
Bolz Hanno J.
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22532
Subject(s) - dbsnp , biology , genetics , missense mutation , 1000 genomes project , exome sequencing , nonsense mutation , exome , nonsense , gene , population , mutation , single nucleotide polymorphism , genotype , medicine , environmental health
MYO1A is considered the gene underlying autosomal dominant nonsyndromic hearing loss DFNA 48 , based on six missense variants, one small in‐frame insertion, and one nonsense mutation. Results from NGS targeting 66 deafness genes in 109 patients identified three families challenging this assumption: two novel nonsense (p.Tyr740* and p.Arg262*) and a known missense variant were identified heterozygously not only in index patients, but also in unaffected relatives. Deafness in these families clearly resulted from mutations in other genes ( MYO 7 A , EYA 1 , and CIB 2 ). Most of the altogether 10 MYO 1 A mutations are annotated in db SNP , and population frequencies (db SNP , 1000 G enomes, E xome S equencing P roject) above 0.1% contradict pathogenicity under a dominant model. One healthy individual was even homozygous for p.Arg262*, compatible with homozygous Myo1a knockout mice lacking any overt pathology. MYO 1 A seems dispensable for hearing and overall nonessential. MYO 1 A adds to the list of “erroneous disease genes”, which will expand with increasing availability of large‐scale sequencing data.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here