A non-sense mutation in the corneodesmosin gene in a Mexican family with hypotrichosis simplex of the scalp
A non-sense mutation in the corneodesmosin gene in a Mexican family with hypotrichosis simplex of the scalp
复制标题
DOI：
10.1111/j.1365-2133.2005.06958.x
复制
发表时间：
2005-12-01
影响因子：
10.3
通讯作者：
Betz, RC
中科院分区：
文献类型：
--
作者：
Dávalos, NO;García-Vargas, A;Betz, RC
背景单纯头皮少毛症(HSS；MIM 146520)是一种罕见的常染色体显性非综合征型脱发，男性和女性的影响均等。到目前为止，只有一小部分家庭被报告患有HSS。受影响的人经历了从童年到成年的弥漫性进行性脱发，仅限于头皮。最近，HSS被定位在6号染色体(6p21.3)的短臂上，使得新桥蛋白基因(CDSN)的突变被确定为这种疾病的原因。目的描述首个具有6代拉丁美洲(墨西哥)背景的HSS家系，并鉴定其CDSN基因突变。结果通过对CDSN基因两个外显子的直接测序，发现该患者外显子2存在无义突变，导致过早终止密码子(Y239X)。PsuI限制性内切酶分析在300条对照染色体中未发现该突变。结论在第一个拉美裔HSS家系中发现了一种无义突变。我们的数据提供了CDSN基因外显子2的第三个停止突变导致HSS的分子遗传学证据。到目前为止，所有导致HSS的已知无义突变都聚集在一个40个氨基酸的区域，这与截短的CDSN蛋白聚集体所产生的显性负效应相一致。
Background Hypotrichosis simplex of the scalp (HSS; MIM 146520) is a rare autosomal dominant form of non-syndromic alopecia that affects men and women equally. Up to now, only a small number of families with HSS have been reported. The affected individuals experience a diffuse progressing hair loss from childhood to adulthood that is confined to the scalp. Recently, HSS has been mapped to the short arm of chromosome 6 (6p21.3), allowing mutations in the corneodesmosin gene (CDSN) to be identified as the cause of the disorder. To date, two stop mutations have been found in three unrelated families with HSS of different ethnic origin.Objectives To describe the first HSS-family with Latin American (Mexican) background comprising 6 generations and to identify a mutation in the CDSN gene.Patients and Methods The patients were examined by a clinician and blood samples were taken. After DNA extraction, sequencing analysis of the CDSN gene and restriction enzyme analysis with PsuI were performed.Results By direct sequencing of the two exons of the CDSN gene, a nonsense mutation was identified in the index patient in exon 2, resulting in a premature stop codon (Y239X). The mutation cosegregates perfectly in the family with the disease and was not found in 300 control chromosomes using a restriction enzyme analysis with PsuI.Conclusions A nonsense mutation was identified in the first family with HSS of Latin American ethnical background. Our data provide molecular genetic evidence for a 3rd stop mutation in exon 2 of the CDSN gene being responsible for HSS. All to date known nonsense mutations responsible 3 for HSS are clustered in a region of 40 amino acids which is in accordance with a dominant negative effect conferred by aggregates of truncated CDSN proteins.