A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene
A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene
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DOI：
10.1038/79178
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发表时间：
2000-09-01
期刊：
影响因子：
30.8
通讯作者：
Glaser, B
中科院分区：
文献类型：
--
作者：
Bitner-Glindzicz, M;Lindley, KJ;Glaser, B
1型引座者综合征描述了深度先天性感觉神经性耳聋、前庭功能减退和儿童发作性视网膜色素变性之间的关系(1)。它是一种常染色体隐性遗传疾病，根据连锁分析将其细分为1A型到1E型(参考文献2-6)，Usher型1C型映射到包含编码ATP敏感K+(KATP)通道成分的基因ABCC8和KCNJ11的区域，这两个基因在高胰岛素血症患者中可能发生突变(7-10)。我们鉴定了来自两个血缘家庭的三名个体，他们患有严重的高胰岛素血症、严重的先天性感音神经性耳聋、肠病和肾小管功能障碍。该疾病的分子基础是11p14-15的122kb纯合子缺失。它包括ABCC8的一部分，并与Usher综合征1C和DFNB18的基因座重叠。11)。这种缺失的着丝粒边界包括在1C型Usher综合征家系中突变的基因的一部分，因此被命名为USH1C。USH1C蛋白的表达模式与邻接性基因缺失和孤立的Usher型1C患者的临床特征一致。
Usher syndrome type 1 describes the association of profound, congenital sensorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa(1). It is an autosomal recessive condition and is subdivided on the basis of linkage analysis into types 1A through 1E (refs 2-6), Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding components of ATP-sensitive K+ (KATP) channels), which may be mutated in patients with hyperinsulinism(7-10). We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction. The molecular basis of the disorder is a homozygous 122-kb deletion of 11p14-15. which includes part of ABCC8 and overlaps with the locus for Usher syndrome type 1C and DFNB18 (ref. 11). The centromeric boundary of this deletion includes part of a gene shown to be mutated in families with type 1C Usher syndrome, and is hence assigned the name USH1C. The pattern of expression of the USH1C protein is consistent with the clinical features exhibited by individuals with the contiguous gene deletion and with isolated Usher type 1C.