背景:我们报道了一个大家族的中国汉族患者患有多汗性外胚层发育不良(HED),GJB6有变异(c.31G>A)。患者家族有不同程度的临床表现三联征。尽管已经报道了相同的变异位点,这个家族的临床表现很难与先天性厚指甲疾病区分开来,掌plant角化病,和先天性毛发减少症.
方法:这项调查涉及一个由五代人组成的46名成员组成的大型中国家庭,包括12名HED患者。先证者(IV4)是男性患者,汗腺功能和牙齿发育正常,没有骨骼发育不良,没有认知障碍,也没有听力障碍.他的父母没有血缘关系。先证者体格检查发现头发稀疏,灰黄色指甲和脚趾甲增厚,有一些纵向脊,除了轻度的双侧掌足底角化过度。GJB6,GJB2和GJA1已被报道为HED的致病基因;因此,我们对患者的样本进行了这三个基因的Sanger测序。在这个家庭里,变异位点在GJB6(c.31G>A,p.Gly11Arg)。建立野生型GJB6及其变异体的过表达载体并转染HaCaT细胞模型,用实时逆转录聚合酶链反应和Westernblot检测相关的mRNA和蛋白表达变化,分别。
结论:我们报告了另一种与GJB6变异相关的HED表型,这可以帮助临床医生诊断HED,尽管其表现不同。
BACKGROUND: We report on a large family of Chinese Han individuals with hidrotic ectodermal dysplasia (HED) with a variation in GJB6 (c.31G>A). The patients in the family had a triad of clinical manifestations of varying degrees. Although the same variation locus have been reported, the clinical manifestations of this family were difficult to distinguish from those of congenital thick nail disorder, palmoplantar keratosis, and congenital hypotrichosis.
METHODS: This investigation involved a large Chinese family of 46 members across five generations and included 12 patients with HED. The proband (IV4) was a male patient with normal sweat gland function and dental development, no skeletal dysplasia, no cognitive disability, and no hearing impairments. His parents were not consanguineously married. Physical examination of the proband revealed thinning hair and thickened grayish-yellow nails and toenails with some longitudinal ridges, in addition to mild bilateral palmoplantar hyperkeratosis. GJB6, GJB2, and GJA1 have been reported to be the causative genes of HED; therefore, we subjected the patient\'s samples to Sanger sequencing of these three genes. In this family, the variation locus was at GJB6 (c.31G>A, p.Gly11Arg). Overexpression vectors of wild-type GJB6 and its variants were established and transfected into HaCaT cell models, and the related mRNA and protein expression changes were determined using real-time reverse transcriptase-polymerase chain reaction and Western blot, respectively.
CONCLUSIONS: We report another HED phenotype associated with GJB6 variations, which can help clinicians to diagnose HED despite its varying presentations.