A novel deletion mutation in the DSG4 gene underlies autosomal recessive hypotrichosis with variable phenotype in two unrelated consanguineous families
A novel deletion mutation in the DSG4 gene underlies autosomal recessive hypotrichosis with variable phenotype in two unrelated consanguineous families
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DOI：
10.1111/ced.12457
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发表时间：
2015-01-01
影响因子：
4.1
通讯作者：
Ahmad, W.
中科院分区：
文献类型：
--
作者：
Ullah, A.;Raza, S. I.;Ahmad, W.
背景常染色体隐性遗传性少毛症是一种罕见的人类遗传性疾病，表现为稀疏的头皮毛发或发生在身体各个部位的羊毛状毛发。迄今为止，已报道了各种形式的孤立性少毛症。据报道，至少有11个基因的突变会导致少毛症。目的探讨两个无关的近亲家庭中常染色体隐性遗传性少毛症的临床和遗传基础。方法通过高度多态性微卫星标记进行基因分型，确定这两个家族与染色体18q21上的DSG4基因的连锁。对DSG4基因的外显子和内含子-外显子边界进行PCR扩增，并对产物进行测序，寻找致病序列变异。结果临床调查显示，其中一个家族的受影响成员出现典型的少毛症，而其他受影响成员则出现念珠菌样头皮毛发。 DSG4 的序列分析揭示了两个家族的受影响受试者中存在一种新的缺失突变 (c.85-1_191del)。结论这项研究进一步扩展了 DSG4 基因突变导致少毛症和念珠菌样头皮毛发的证据。
BackgroundAutosomal recessive hypotrichosis is a rare human hereditary disorder presenting as sparse scalp hair or as woolly hair occurring on various parts of the body. Various forms of isolated hypotrichosis have been reported to date. Mutations in at least 11 genes have been reported to cause hypotrichosis.AimsTo investigate the clinical and genetic basis of autosomal recessive hypotrichosis in two unrelated consanguineous families.MethodsGenotyping by highly polymorphic microsatellite markers established linkage in both families to the DSG4 gene on chromosome 18q21. PCR amplification of exons and intron-exon borders of the DSG4 gene was performed, and the products sequenced to search for disease-causing sequence variants.ResultsClinical investigation revealed typical hypotrichosis in the affected members of one family, while other affected members showed presence of monilethrix-like scalp hair. Sequence analysis of DSG4 revealed a novel deletion mutation (c.85-1_191del) in the affected subjects of both families.ConclusionsThis study further extends the body of evidence that mutations in the DSG4 gene result in both hypotrichosis and monilethrix-like scalp hair.