Mutations in the desmoglein 4 gene underlie localized autosomal recessive hypotrichosis with monilethrix hairs and congenital scalp erosions
Mutations in the desmoglein 4 gene underlie localized autosomal recessive hypotrichosis with monilethrix hairs and congenital scalp erosions
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DOI：
10.1038/sj.jid.5700237
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发表时间：
2006-06-01
影响因子：
6.5
通讯作者：
Christiano, Angela M.
中科院分区：
文献类型：
--
作者：
Schaffer, Julie V.;Bazzi, Hisham;Christiano, Angela M.
局限性常染色体隐性遗传性毛发减少症（LAH）是一种新近定义的疾病，其特征是头皮、躯干和四肢上的毛发脆弱、短而稀疏。桥粒芯糖蛋白4（DSG 4）是桥粒钙粘蛋白家族的一个新成员，在毛囊和基底上表皮中表达，已发现其突变是LAH的基础。到目前为止，等位基因系列包括在受影响的Pakastani kindergarten中鉴定的复发性基因内缺失和在伊拉克家庭中检测到的错义突变。我们报告了三个兄弟姐妹的伊拉克和伊朗血统的LAH提出了先天性头皮糜烂和念珠状头发，以前没有描述过这种疾病的功能。毛囊角化过度性丘疹和明显瘙痒也是突出的临床表现。新的复合杂合DSG 4突变，包括剪接位点突变和破坏细胞外（EC）2-EC 3界面中保守的钙结合位点的错义突变，被发现是该家族疾病的基础。这些观察结果拓宽了LAH的表型和基因型谱，进一步说明了DSG 4功能障碍对表皮和毛干完整性的影响。
Localized autosomal recessive hypotrichosis (LAH) is a recently defined disorder characterized by fragile, short, sparse hairs on the scalp, trunk, and extremities. Mutations in desmoglein 4 (DSG4), a novel member of the desmosomal cadherin family that is expressed in the hair follicle as well as the suprabasal epidermis, have been found to underlie LAH. Thus far, the allelic series includes a recurrent intragenic deletion identified in affected Pakastani kindreds and a missense mutation detected in an Iraqi family. We report three siblings of Iraqi and Iranian origin with LAH that presented with congenital scalp erosions and monilethrix-like hairs, features that have not been previously described in this disorder. Follicular hyperkeratotic papules and marked pruritus were also prominent clinical findings. Novel compound heterozygous DSG4 mutations, including a splice-site mutation and a missense mutation that disrupts a conserved calcium-binding site in the extracellular (EC)2-EC3 interface, were found to underlie the disease in this family. These observations broaden the phenotypic and genotypic spectrum of LAH, further illustrating the consequences of DSG4 dysfunction on epidermal and hair shaft integrity.