Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q
Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q
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DOI：
10.1086/302858
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发表时间：
2000-04-01
影响因子：
9.8
通讯作者：
Ajlouni, K
中科院分区：
文献类型：
--
作者：
El-Shanti, H;Lidral, AC;Ajlouni, K
Wolfram综合征，有时也被称为“DIDMOAD”（尿崩症、糖尿病、视神经萎缩和耳聋），是一种常染色体隐性遗传神经退行性疾病，其诊断仅需胰岛素依赖型糖尿病和视神经萎缩。研究人员已经将Wolfram综合征定位于染色体4p16.1，最近，已经克隆了一种编码假定跨膜蛋白的基因，并在患者中发现了突变。为了探讨基因座异质性的可能性，招募了来自四个不同家庭的16名患者。这些具有Wolfram综合征表型的患者还具有先前未报道的其他特征。所有受影响的家庭成员均无尿崩症。此外，一些患者有严重的上消化道溃疡和出血。使用三个微卫星标记（D4 S432，D4 S3023，和D4 S2366）被报道与染色体4p16.1位点，我们显着排除了连锁的恐惧三个家庭。在一个家庭中的两个受影响的个人表现出纯合性的所有三个标记的连锁区域的染色体4p16.1。对于其他三个家庭，Wolfram综合征的遗传异质性通过证明与染色体4 q22 -24的连锁来验证。总之，我们报告了16例Wolfram综合征患者的独特临床表现和连锁分析结果，并为这种疾病的遗传异质性提供了进一步的证据。我们还提供了一个新的基因座，在胰岛素依赖型糖尿病的病因中发挥作用的数据。
Wolfram syndrome, which is sometimes referred to as "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an autosomal recessive neurodegenerative disorder for which only insulin-dependent diabetes mellitus and optic atrophy are necessary to make the diagnosis. Researchers have mapped Wolfram syndrome to chromosome 4p16.1, and, recently, a gene encoding a putative transmembrane protein has been cloned and mutations have been identified in patients. To pursue the possibility of locus heterogeneity, 16 patients from four different families were recruited. These patients, who have the Wolfram syndrome phenotype, also have additional features that have not previously been reported. There is an absence of diabetes insipidus in all affected family members. In addition, several patients have profound upper gastrointestinal ulceration and bleeding. With the use of three microsatellite markers (D4S432, D4S3023, and D4S2366) reported to be linked to the chromosome 4p16.1 locus, we significantly excluded linkage in three of the fear families. The two affected individuals in one family showed homozygosity for all three markers from the region of linkage on chromosome 4p16.1. For the other three families, genetic heterogeneity for Wolfram syndrome was verified by demonstration of linkage to chromosome 4q22-24. In conclusion, we report the unique clinical findings and linkage-analysis results of 16 patients with Wolfram syndrome and provide further evidence for the genetic heterogeneity of this disorder. We also provide data on a new locus that plays a role in the etiology of insulin-dependent diabetes mellitus.