伴皮肤鳞状细胞癌的角膜炎-鱼鳞病-耳聋综合征一例GJB2基因突变研究并文献复习

A case of keratitis-ichthyosis-deafness syndrome complicated by cutaneous squamous cell carcinoma：mutation analysis of the GJB2 gene and literature review

目的：以 GJB2基因为候选基因，研究1例伴有皮肤鳞状细胞癌的角膜炎-鱼鳞病-耳聋综合征患者的分子病因。方法收集1例伴有皮肤鳞状细胞癌的角膜炎-鱼鳞病-耳聋综合征患者临床资料，提取患者及其父母的外周血 DNA，用 PCR 扩增 GJB2基因的第2外显子后直接测序，检测患者 GJB2基因的突变情况。结果患者 GJB2基因中核苷酸序列外显子2第148位碱基由 G 突变为 A（c.148G 〉 A），此突变导致 GJB2基因第50位氨基酸密码子由 GAC 替换为 AAC，其编码的连接蛋白 Cx26第50位天冬氨酸转换成天冬酰胺（p.Asp50Asn）。此外，GJB2基因外显子2第79位碱基由 G 突变为 A（c.79G 〉 A），突变导致连接蛋白 Cx26第27位的缬氨酸转换成异亮氨酸（p.Val27Ile）。患者的父母未检测到 GJB2基因突变位点。文献检索发现国外已有13例角膜炎-鱼鳞病-耳聋综合征伴皮肤黏膜鳞状细胞癌的病例报道，经过基因测序确诊的7例患者均为 GJB2基因 c.148G 〉 A 突变。结论 GJB2基因突变可能是导致本例角膜炎-鱼鳞病-耳聋综合征临床表型的致病原因，c.148G 〉 A 突变位置可能与皮肤鳞状细胞癌发生有关。

Objective To analyze mutations in the GJB2 gene in a Chinese patient with keratitis-ichthyosis-deafness （KID）syndrome complicated by cutaneous squamous cell carcinoma. Methods Clinical data were collected from a patient with KID syndrome complicated by cutaneous squamous cell carcinoma. Peripheral blood samples were obtained from the patient and her parents, and DNA was extracted from these blood samples. PCR was performed to amplify the exon 2 of the GJB2 gene followed by direct DNA sequencing. Results A mutation （c.148G 〉 A）was identified at position 148 in exon 2 of the GJB2 gene, which caused a codon change from GAC to AAC and resulted in the substitution of aspartate by asparagine at position 50 in the connexin26 （Cx26）protein （p.Asp50Asn）. Inaddition,anothermutation（c. 79G 〉 A）, which led to the substitution of valine by isoleucine at codon 27 in Cx26 （p.Val27Ile）, was found at position 79 in exon 2 of the GJB2 gene. Neither of the two mutations was detected in the patient′s parents. Literature review revealed that 13 cases of KID syndrome complicated by cutaneous squamous cell carcinoma had been reported in abroad, and the mutation c.148G 〉 A was detected in the GJB2 gene in all the 7 cases finally diagnosed by gene sequencing. Conclusion GJB2 gene mutations may be responsible for the clinical phenotype of KID syndrome in this Chinese patient, and the mutation c.148G 〉 A may be related to the development of cutaneous squamous cell carcinoma.