Höglund P, Auranen M, Socha J, Popinska K, Nazer H, Rajaram U, Al Sanie A, Al-Ghanim M, Holmberg C, de la Chapelle A, Kere J
Department of Medical Genetics, University of Helsinki, Finland.
Am J Hum Genet. 1998 Sep;63(3):760-8. doi: 10.1086/301998.
Congenital chloride diarrhea (CLD) is an inherited intestinal disorder caused by mutations in the down-regulated in adenoma gene. In Finland, the disease is prevalent because of a founder effect, and all but one of the CLD-associated chromosomes carry the same mutation, V317del. In Poland, another area with a high incidence of CLD, as many as seven different mutations have been detected so far. A third known cluster of CLD, around the Persian Gulf, has not been genetically studied. We studied the allelic diversity of CLD in Poland, in Saudi Arabia and Kuwait, and in three isolated families from North America and Hong Kong. Altogether, eight novel mutations were identified, making a total of 19 known CLD gene mutations. The Polish major mutation I675-676ins was found in 47% of the Polish CLD-associated chromosomes. Haplotype analysis and clustering of the I675-676ins mutation supported a founder effect and common ancestral origin. As in Finland, a major founder effect was observed in Arab patients: 94% of the CLD-associated chromosomes carried a nonsense mutation, G187X, which occurred in either a conserved ancestral haplotype or its derivative. Our data confirm that the same locus is mutated in all cases of CLD studied so far. In Poland, a relatively common founder mutation is likely to highlight a set of rare mutations that would very rarely produce homozygosity alone. This suggests that mutations in the CLD locus are not rare events. Although the disease is thought to be rare, undiagnosed patients may not be uncommon.
先天性氯腹泻（CLD）是一种由腺瘤下调基因（down-regulated in adenoma gene）突变引起的遗传性肠道疾病。在芬兰，由于奠基者效应，该病较为普遍，除一条外，所有与CLD相关的染色体都携带相同的突变，即V317del。在波兰，另一个CLD高发地区，迄今为止已检测到多达七种不同的突变。已知的第三个CLD聚集区位于波斯湾周边，但尚未进行基因研究。我们研究了波兰、沙特阿拉伯和科威特以及来自北美和香港的三个孤立家族中CLD的等位基因多样性。总共鉴定出八个新突变，使已知的CLD基因突变总数达到19个。波兰主要突变I675 - 676ins在47%的波兰CLD相关染色体中被发现。I675 - 676ins突变的单倍型分析和聚类支持了奠基者效应和共同的祖先起源。与芬兰一样，在阿拉伯患者中也观察到了主要的奠基者效应：94%的CLD相关染色体携带一个无义突变G187X，该突变发生在一个保守的祖先单倍型或其衍生物中。我们的数据证实，迄今为止研究的所有CLD病例中，相同的基因座发生了突变。在波兰，一个相对常见的奠基者突变可能凸显出一组罕见突变，这些突变单独出现时很少会产生纯合性。这表明CLD基因座的突变并非罕见事件。尽管该病被认为很罕见，但未被诊断的患者可能并不少见。
