CLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews,Clinical Genetics

当前位置： X-MOL 学术 › Clin. Genet. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

CLDN1 Arg81His founder variant causes ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC) syndrome in Moroccan Jews
Clinical Genetics ( IF 2.9 ) Pub Date : 2023-10-09 , DOI: 10.1111/cge.14432
Marina Eskin-Schwartz _{1,

2} , Vadim Dolgin ₃ , Elena Didkovsky ₄ , Ilana Aminov ₃ , Anna Pikovsky ₅ , Noam Hadar ₃ , Eyal Kristal ₆ , Galina Ling _{6,

7} , Idan Cohen ₈ , Uri Zilberman ₉ , Ohad S Birk _{1,

2,

3}

Affiliation

Neonatal ichthyosis and sclerosing cholangitis syndrome (NISCH), also known as ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC), is an extremely rare disease of autosomal recessive inheritance, resulting from loss of function of the tight junction protein claudin-1. Its clinical presentation is highly variable, and is characterized by liver and ectodermal involvement. Although most ILVASC cases described to date were attributed to homozygous truncating variants in CLDN1, a single missense variant CLDN1 p.Arg81His, associated with isolated skin ichthyosis phenotype, has been recently reported in a family of Moroccan Jewish descent. We now describe seven patients with ILVASC, originating from four non consanguineous families of North African Jewish ancestry (including one previously reported family), harboring CLDN1 p.Arg81His variant, and broaden the phenotypic spectrum attributed to this variant to include teeth, hair, and liver/bile duct involvement, characteristic of ILVASC. Furthermore, we provide additional evidence for pathogenicity of the CLDN1 p.Arg81His variant by transmission electron microscopy of the affected skin, revealing distorted tight junction architecture, and show through haplotype analysis in the vicinity of the CLDN1 gene, that this variant represents a founder variant in Jews of Moroccan descent with an estimated carrier frequency of 1:220.

中文翻译：

CLDN1 Arg81His 创始人变异导致摩洛哥犹太人出现鱼鳞病、白细胞空泡、脱发和硬化性胆管炎 (ILVASC) 综合征

新生儿鱼鳞病和硬化性胆管炎综合征（NISCH），也称为鱼鳞病、白细胞空泡、脱发和硬化性胆管炎（ILVASC），是一种极其罕见的常染色体隐性遗传疾病，由紧密连接蛋白claudin-1功能丧失所致。其临床表现变化很大，以肝脏和外胚层受累为特征。尽管迄今为止描述的大多数 ILVASC 病例归因于CLDN1中的纯合截短变异，但最近在一个摩洛哥犹太血统家庭中报道了与孤立的皮肤鱼鳞病表型相关的单个错义变异 CLDN1 p.Arg81His。我们现在描述了七名 ILVASC 患者，来自四个北非犹太血统的非近亲家庭（包括一个先前报道的家庭），携带 CLDN1 p.Arg81His 变异，并扩大了归因于该变异的表型谱，包括牙齿、头发和肝/胆管受累，这是 ILVASC 的特征。此外，我们通过受影响皮肤的透射电子显微镜，揭示了扭曲的紧密连接结构，为 CLDN1 p.Arg81His 变体的致病性提供了额外的证据，并通过CLDN1基因附近的单倍型分析表明，该变体代表了一个创始人变体摩洛哥血统的犹太人，估计携带频率为 1:220。

更新日期：2023-10-09

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南