Department of Dermatology, Maastricht University Medical Centre, PO BOX 5800, 6202 AZ Maastricht, the Netherlands.
Br J Dermatol. 2010 Jul;163(1):205-7. doi: 10.1111/j.1365-2133.2010.09794.x.
Neonatal ichthyosis-sclerosing cholangitis (NISCh) syndrome is a rare autosomal recessive disorder associated with scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis. It is caused by homozygous mutations in the CLDN1 gene coding for the tight junction component claudin-1. Only five patients have been reported so far: four patients from two inbred Moroccan families, all carrying a dinucleotide deletion c.200_201delTT in the CLDN1 gene and a Swiss patient with a 1-bp deletion (c.358delG) in exon 2. Here, we report on three Moroccan brothers born of consanguineous parents (first cousins) presenting with ichthyosis, hypotrichosis and congenital paucity of bile ducts. In our patients, we found the same dinucleotide deletion (c.200_201delTT) in the CLDN1 gene that had been reported previously. In our view, this is suggestive of a founder effect. Interestingly, our patients presented not with sclerosing cholangitis but with congenital paucity of bile ducts. Although the two conditions cannot always be easily distinguished, we would suggest that paucity of bile ducts could be a manifestation of NISCh.
新生儿鱼鳞病-硬化性胆管炎（NISCh）综合征是一种罕见的常染色体隐性遗传病，与头皮毛发稀疏、瘢痕性脱发、鱼鳞病和硬化性胆管炎有关。它是由 CLDN1 基因编码紧密连接成分 Claudin-1 的纯合突变引起的。迄今为止，仅报道了五名患者：来自两个近亲摩洛哥家庭的四名患者，均携带 CLDN1 基因中的二核苷酸缺失 c.200_201delTT，以及一名瑞士患者携带外显子 2 中的 1 个碱基缺失（c.358delG）。在这里，我们报告了三名来自近亲（表亲）父母的摩洛哥兄弟，他们表现为鱼鳞病、毛发稀疏和先天性胆管稀少。在我们的患者中，我们发现了 CLDN1 基因中与之前报道的相同的二核苷酸缺失（c.200_201delTT）。在我们看来，这表明存在一个奠基者效应。有趣的是，我们的患者没有表现出硬化性胆管炎，而是表现为先天性胆管稀少。尽管这两种情况并不总是容易区分，但我们认为胆管稀少可能是 NISCh 的一种表现。
