A novel compound heterozygous mutation in the <i>GJB2</i> gene is associated with non-syndromic hearing loss in a Chinese family

Abstract

Autosomal recessive (AR) non-syndromic hearing loss (NSHL) is the most common form of hereditary deafness. Mutations in the gap junction protein beta 2 (GJB2) gene encoding connexin 26 (Cx26) account for about 50% of cases of ARNSHL. In the current study, a combination of exome sequencing and Sanger sequencing in a Chinese Dong family with ARNSHL allowed identification of a novel compound heterozygous mutation c.240G>C(p. Q80H)/C.109G>A(p.V37I) in exon 2 of the GJB2 gene, which co-segregated with the disease phenotype in this family and was not evident in 100 healthy controls. Bioinformatic analysis revealed that the two mutations in the GJB2 gene were probably pathogenic. Results indicated that the compound heterozygous variants, p.Q80H and p.V37I, in the GJB2 gene are associated with ARNSHL. The Q80H variant was initially identified in patients of Dong Chinese origin with NSHL. The current results broaden the spectrum of GJB2 mutations responsible for NSHL and have important implications for molecular diagnosis, treatment, and genetic counseling for this family.

GJB2 mutations in Iranian Azeri population with autosomal recessive nonsyndromic hearing loss (ARNSHL): First report of c.238 C>A mutation in Iran

“…To date, four missense mutations (Q80K, Q80P, Q80R, and Q80H) and one nonsense mutation were reported at this position, which lead to HL and can be considered in the screening, identification, and study of people with deafness. 43 Therefore, this novel mutation in the GJB2 gene appears to cause HL in the Iranian population, especially in the Azeri population. Therefore, the mutation screening of GJB2 for c.238C>A; p. Gln80Lys is recommended in patients with HL, belonging to the Azeri ethnic group.…”

Case report of a novel mutation in the TNC gene in Chinese patients with nonsyndromic hearing loss

“…Different amino acids have different structures, and the chemical bonds around amino acids may also change after the mutation of amino acids, which affects the change of protein structure and then affects protein function. [23–26] The 3D model was constructed for structural analysis of WT/Mut TNC and TBC1D24 proteins to determine the pathogenicity of mutant TNC and TBC1D24 according to SWISS MODEL and AlphaFold online prediction program. Structural modeling demonstrated that the p.Thr951Ile and p.Arg524Trp variants altered the normal protein structure (Fig.…”

Analysis of deafness susceptibility gene of neonates in northern Guangdong, China

“…The ClinGen hearing loss expert panel determined that c.109G>A is a causative factor for autosomal recessive non-syndromic hearing loss with variable expression and incomplete penetrance 14 . According to ACMG, the c.109G>A variant is predicted to be a pathogenic variant 15 . In this study, five patients with the c.109G>A homozygous variant and two with heterozygous variants did not www.nature.com/scientificreports/ pass hearing screening.…”