Primignani P, Castorina P, Sironi F, Curcio C, Ambrosetti U, Coviello D A
Dipartimento di Medicina di Laboratorio-Laboratorio di Genetica Medica, A.O. Istituti Clinici di Perfezionamento, Milan, Italy.
Clin Genet. 2003 Jun;63(6):516-21. doi: 10.1034/j.1399-0004.2003.00079.x.
Mutations of the GJB2 gene, encoding Connexin 26, are the most common cause of hereditary congenital hearing loss in many countries, and account for up to 50% of cases of autosomal-recessive non-syndromic deafness. By contrast, only a few GJB2 mutations have been reported to cause an autosomal-dominant form of non-syndromic deafness. We report on a family from southern Italy in whom dominant, non-syndromic, post-lingual hearing loss is associated with a novel missense mutation in the GJB2 gene. Direct sequencing of the gene showed a heterozygous G-->A transition at nucleotide 535, resulting in an aspartic acid to asparagine amino acid substitution at codon 179 (D179N). This mutation occurred in the second extracellular domain (EC2), which would seem to be very important for connexon-connexon interaction.
编码连接蛋白26的GJB2基因突变是许多国家遗传性先天性听力损失的最常见原因，在常染色体隐性非综合征性耳聋病例中占比高达50%。相比之下，仅有少数GJB2基因突变被报道可导致常染色体显性形式的非综合征性耳聋。我们报告了一个来自意大利南部的家族，该家族中显性、非综合征性、语后听力损失与GJB2基因的一个新的错义突变相关。对该基因进行直接测序显示，在核苷酸535处发生了G→A转换，导致密码子179处的天冬氨酸被天冬酰胺取代（D179N）。此突变发生在第二个细胞外结构域（EC2），这似乎对连接子 - 连接子相互作用非常重要。
