rs998045226

This systematic review synthesizes the genetic epidemiology of non-syndromic hearing impairment (NSHI) in Europe, analyzing mutation screening studies from multiple countries. DFNB1 (GJB2) is the most common autosomal recessive form (11-57% of cases, with c.35delG accounting for 58-93% of mutations), while STRC accounts for 16% of recessive cases. For autosomal-dominant NSHI, DFNA22 (MYO6) and DFNA8/12 (TECTA) are the most frequent, representing 21% and 18% of elucidated cases respectively. The review identifies over 120 genes involved in NSHI and emphasizes the need for standardized experimental approaches and stratified reporting of results across European populations.

This study characterizes the spectrum of GJB2 (Connexin 26) mutations causing DFNB1 autosomal recessive deafness in 1,294 deaf individuals. Among 205 DFNB1 cases identified, the c.35delG deletion accounts for most alleles, with homozygotes showing 88% mean hearing impairment and severe-to-profound deafness in ~90% of cases, while individuals with two missense mutations show only 37% mean impairment (P<0.05). The study also identified non-coding mutations including c.1-3172G>A and del(GJB6-D13S1830), and validated DHPLC as a highly sensitive (98.1%) mutation screening method.

Screening of 204 Austrian patients with non-syndromic hearing loss identified GJB2 mutations in 31 patients (15.2%), with c.35delG accounting for 72.1% of disease alleles. The c.35delG carrier frequency was 0.9% (1/110) in 1,212 control subjects. L90P (c.269T>C) was identified as a pathogenic mutation (9.8% of disease alleles) that typically confers a mild-to-moderate phenotype when compound heterozygous. Progressive hearing loss and recurrent sudden sensorineural hearing loss were documented in patients with the c.35delG/L90P genotype.