Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population
Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population
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DOI：
10.1007/s00439-004-1227-2
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发表时间：
2005-03-01
期刊：
影响因子：
5.3
通讯作者：
Liu, XZ
中科院分区：
文献类型：
--
作者：
Ouyang, XM;Yan, D;Liu, XZ
Usher综合征I型（USH 1）是该综合征的最严重形式，其特征在于严重的先天性感觉神经性耳聋、前庭功能障碍和视网膜色素变性。USH 1基因座USH 1A-G分别定位于14 q32、11q13.5、11 p15、10 q21-q22、21 q21、10 q21-q22和17 q24 -25。MYO 7A、USH 1C、CDH 23、PCDH 15和SANS等5个基因的突变分别是Usher综合征1B型、1C型、1D型、1F型和1G型的病因。在本研究中，我们进行了系统的突变筛查USH 1患者从美国和英国的这些基因。我们总共鉴定了27种不同的突变，其中19种是新的，包括9种错义，2种无义，4种缺失，1种插入和3种剪接缺陷。大约35-39%的观察到的突变涉及USH 1B和USH 1D基因，其次是11%的USH 1F和7%的USH 1C在非埃塞俄比亚等位基因和7%的USH 1G。12个MYO 7A突变中的两个，R666 X和IVS 40 -1G>T占该位点突变的38%。193 delC突变占CDH 23（USH 1D）突变的26%，证实了其高频率。本研究中最常见的PCDH 15（USH 1F）突变，5601- 5603 delAAC，占突变等位基因的33%。有趣的是，一种新的SANS突变W38 X仅在美国队列中观察到。目前的研究表明，MYO 7A和CDH 23突变是USH 1的两个主要原因，而PCDH 15，USH 1C和SANS是不太常见的原因。
Usher syndrome type I (USH1), the most severe form of this syndrome, is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. At least seven USH1 loci, USH1A-G, have been mapped to the chromosome regions 14q32, 11q13.5, 11p15, 10q21-q22, 21q21, 10q21-q22, and 17q24-25, respectively. Mutations in five genes, including MYO7A, USH1C, CDH23, PCDH15 and SANS, have been shown to be the cause of Usher syndrome type 1B, type 1C, type 1D, type 1F and type 1G, respectively. In the present study, we carried out a systematic mutation screening of these genes in USH1 patients from USA and from UK. We identified a total of 27 different mutations; of these, 19 are novel, including nine missense, two nonsense, four deletions, one insertion and three splicing defects. Approximatelly 35-39% of the observed mutations involved the USH1B and USH1D genes, followed by 11% for USH1F and 7% for USH1C in non-Acadian alleles and 7% for USH1G. Two of the 12 MYO7A mutations, R666X and IVS40-1G>T accounted for 38% of the mutations at that locus. A 193delC mutation accounted for 26% of CDH23 (USH1D) mutations, confirming its high frequency. The most common PCDH15 (USH1F) mutation in this study, 5601-5603delAAC, accounts for 33% of mutant alleles. Interestingly, a novel SANS mutation, W38X, was observed only in the USA cohort. The present study suggests that mutations in MYO7A and CDH23 are the two major components of causes for USH1, while PCDH15, USH1C, and SANS are less frequent causes.