Höglund P, Haila S, Gustavson K H, Taipale M, Hannula K, Popinska K, Holmberg C, Socha J, de la Chapelle A, Kere J
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
Hum Mutat. 1998;11(4):321-7. doi: 10.1002/(SICI)1098-1004(1998)11:4<321::AID-HUMU10>3.0.CO;2-A.
An inherited defect in intestinal anion exchange, congenital chloride diarrhea (CLD), was recently shown to be caused by mutations in the down-regulated in adenoma (DRA) gene. A three base pair deletion resulting in the loss of an amino acid valine (V317del) in the predicted CLD/DRA protein was shown to be responsible for all CLD cases in a Finnish founder population. Two additional mutations, H124L and 344delT, were found in Polish CLD patients. Here, we screened for additional mutations in a set of 14 CLD families of Polish, Swedish, North American, and Finnish origin using primers that allowed mutation searches directly from genomic DNA samples. We found eight novel mutations in the CLD/DRA gene. The mutations included two transversions, one transition, one insertion, and four small deletions. Of 11 sequence alterations detected so far, nine lie clustered in three short segments that are 49 bp, 39 bp, and 65 bp in size, respectively. These short segments span only 6.7% of the total cDNA length, suggesting functional importance or mutation-prone DNA regions of the corresponding CLD/DRA protein domains.
肠道阴离子交换的一种遗传性缺陷，即先天性氯化物腹泻（CLD），最近被证明是由腺瘤下调基因（DRA）的突变引起的。在芬兰一个奠基者群体中，一个导致预测的CLD/DRA蛋白中一个缬氨酸（V317del）缺失的三碱基对缺失被证明是所有CLD病例的病因。在波兰CLD患者中发现了另外两个突变，即H124L和344delT。在此，我们使用能够直接从基因组DNA样本中搜索突变的引物，对一组来自波兰、瑞典、北美和芬兰的14个CLD家族进行了额外突变的筛查。我们在CLD/DRA基因中发现了8个新突变。这些突变包括两个颠换、一个转换、一个插入和四个小缺失。在迄今检测到的11个序列改变中，9个集中在三个短片段中，其大小分别为49 bp、39 bp和65 bp。这些短片段仅占cDNA总长度的6.7%，表明相应CLD/DRA蛋白结构域具有功能重要性或易发生突变的DNA区域。
