The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome
The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome
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DOI：
10.1086/510499
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发表时间：
2007-01-01
影响因子：
9.8
通讯作者：
Attie-Bitach, Tania
中科院分区：
文献类型：
--
作者：
Baala, Lekbir;Romano, Stephane;Attie-Bitach, Tania
Joubert综合征（JS）是一种常染色体隐性遗传疾病，其特征是小脑蚓部发育不全，伴有张力减退、发育迟缓、异常呼吸模式和异常眼球运动。视网膜营养不良和肾脏异常的关联定义了JS B型。JS是一种遗传异质性疾病，迄今已鉴定出两个基因AHI 1和CEP 290突变。此外，在轻度小脑和脑干异常的患者亚组中发现了与引起青少年肾单位营养不良相同的NPHP 1缺失。在一些JS患者中偶尔报告枕叶脑膨出和/或多指（趾）畸形，这些表型特征也可在Meckel-Gruber综合征（MKS）中观察到。MKS是一种罕见的常染色体隐性致死性疾病，其特征为中枢神经系统畸形（通常为枕部脑膜脑膨出）、轴后多指（趾）畸形、多囊性肾发育不良和肝门管区导管增生。由于JS和MKS之间有明显的表型重叠，我们假设最近发现的MKS基因突变，染色体17 q上的MKS 1和8 q上的MKS 3，可能是JS的原因。在对一系列JS患者（n = 22）进行MKS 1和MKS 3突变分析后，我们在4例JS患者中鉴定了MKS 3突变，从而将MKS 3定义为第六个JS位点（JBTS 6）。在该系列中未鉴定到MKS 1突变，表明等位性仅限于MKS 3。
Joubert syndrome (JS) is an autosomal recessive disorder characterized by cerebellar vermis hypoplasia associated with hypotonia, developmental delay, abnormal respiratory patterns, and abnormal eye movements. The association of retinal dystrophy and renal anomalies defines JS type B. JS is a genetically heterogeneous condition with mutations in two genes, AHI1 and CEP290, identified to date. In addition, NPHP1 deletions identical to those that cause juvenile nephronophthisis have been identified in a subset of patients with a mild form of cerebellar and brainstem anomaly. Occipital encephalocele and/or polydactyly have occasionally been reported in some patients with JS, and these phenotypic features can also be observed in Meckel-Gruber syndrome (MKS). MKS is a rare, autosomal recessive lethal condition characterized by central nervous system malformations ( typically, occipital meningoencephalocele), postaxial polydactyly, multicystic kidney dysplasia, and ductal proliferation in the portal area of the liver. Since there is obvious phenotypic overlap between JS and MKS, we hypothesized that mutations in the recently identified MKS genes, MKS1 on chromosome 17q and MKS3 on 8q, may be a cause of JS. After mutation analysis of MKS1 and MKS3 in a series of patients with JS (n = 22), we identified MKS3 mutations in four patients with JS, thus defining MKS3 as the sixth JS locus (JBTS6). No MKS1 mutations were identified in this series, suggesting that the allelism is restricted to MKS3.