Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems
Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems
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DOI：
10.1086/431244
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发表时间：
2005-07-01
影响因子：
9.8
通讯作者：
Hofstra, RMW
中科院分区：
文献类型：
--
作者：
Brooks, AS;Bertoli-Avella, AM;Hofstra, RMW
通过纯合定位，我们在一个摩洛哥近亲家庭中发现了戈德堡-什普林岑综合征（GOSHS）的10q21.3- q22.1位点。该近交家族的GOSHS的表型特征包括小头畸形和智力低下，这都是中枢神经系统缺陷，以及先天性巨结肠病，一种肠神经系统缺陷。此外，由于该家族的所有患者均被诊断为双侧广泛性多泪，因此该特征也可能被认为是该综合征的关键特征。我们证明，KIAA1279在10q22.1位点的纯合无义突变，编码一个具有两个四聚肽重复的蛋白质，是先天性巨结肠病和广泛性多小脑回综合征的基础，从而确定了KIAA1279在肠和中枢神经系统发育中的重要性。
We identified, by homozygosity mapping, a novel locus on 10q21.3- q22.1 for Goldberg- Shprintzen syndrome ( GOSHS) in a consanguineous Moroccan family. Phenotypic features of GOSHS in this inbred family included microcephaly and mental retardation, which are both central nervous system defects, as well as Hirschsprung disease, an enteric nervous system defect. Furthermore, since bilateral generalized polymicogyria was diagnosed in all patients in this family, this feature might also be considered a key feature of the syndrome. We demonstrate that homozygous nonsense mutations in KIAA1279 at 10q22.1, encoding a protein with two tetratrico peptide repeats, underlie this syndromic form of Hirschsprung disease and generalized polymicrogyria, establishing the importance of KIAA1279 in both enteric and central nervous system development.