R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma

• Published in: International journal of pediatric otorhinolaryngology 2014-09, Vol.78 (9), p.1461-1466
• Main Authors: Jiang, Shu-juan, Di, Zheng-hong, Huang, Dan, Zhang, Jiu-bin, Zhang, Yuan-yuan, Li, Shu-qin, He, Rong
• Format: Article
• Language: English
• Subjects: Adult; Asian Continental Ancestry Group - genetics; China; Connexin 26; Connexins - genetics; De novo mutation; Female; GJB2 gene; Hearing impairment; Hearing Loss, Sensorineural - complications; Hearing Loss, Sensorineural - genetics; Humans; Keratoderma, Palmoplantar - complications; Keratoderma, Palmoplantar - genetics; Male; Middle Aged; Mutation; Palmoplantar keratoderma; Pedigree; Structural analysis
• ISSN: 0165-5876; 1872-8464
• DOI: 10.1016/j.ijporl.2014.06.008

Mutations in the GJB2 gene encoding connexin 26 (Cx26) are major causes of hereditary deafness. This study aimed to characterize the mutation profiles of the GJB2 gene in a Chinese family with sensorineural hearing loss. A Chinese family that included three individuals with sensorineural hearing loss and palmoplantar keratoderma underwent complete physical examinations, audiological examinations including pure tone audiometry and auditory brainstem response, skin pathological examination, and temporal CT scans. The entire coding region of GJB2, GJB3, GJB6, and the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN) were sequenced. Structural analysis was performed to detect the effects of mutation on the tertiary structure of Cx26. A dominant GJB2 mutation, c.224G>A (p.Arg75Gln, p.R75Q), was detected in the family. No other mutation was identified in GJB2, GJB3, GJB6, or the coding exons (exon7+8 and 19) of SLC26A4, mitochondrial 12SrRNA, and tRNA Ser (UCN). Structural analysis revealed that the p.R75Q mutation likely affects the structural stability and permeation properties of the Cx26 gap junction channel. Our findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma.