R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma |
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Authors: | Shu-juan Jiang Zheng-hong Di Dan Huang Jiu-bin Zhang Yuan-yuan Zhang Shu-qin Li Rong He |
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Affiliation: | 1. Clinical Genetics Department, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China;2. Dermatological Department, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China;3. Orthopedics Department, The First Affiliated Hospital, China Medical University, 110001 Shenyang, Liaoning, PR China;4. Virus Laboratory, The Affiliated Shengjing Hospital, China Medical University, 110004 Shenyang, Liaoning, PR China |
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Abstract: | ObjectivesMutations 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.MethodsA 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.ResultsA 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.ConclusionOur findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma. |
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Keywords: | Cx26, connexin26 HL, hearing loss KID, keratitis&ndash ichthyosis&ndash deafness PPK, palmoplantar keratoderma HGVS, human genome variation society PTA, pure tone audiometry ABR, auditory brainstem response CT, temporal computerized tomography CL, cytoplasmic domain EC, extracellular domain TM, transmembrane domains Gj, gap-junctional conductance |
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