Novel USH2A mutations in Japanese Usher syndrome type 2 patients: marked differences in the mutation spectrum between the Japanese and other populations
Novel USH2A mutations in Japanese Usher syndrome type 2 patients: marked differences in the mutation spectrum between the Japanese and other populations
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DOI：
10.1038/jhg.2011.45
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发表时间：
2011-07-01
影响因子：
3.5
通讯作者：
Minoshima, Shinsei
中科院分区：
文献类型：
--
作者：
Nakanishi, Hiroshi;Ohtsubo, Masafumi;Minoshima, Shinsei
Usher综合征（USH）是一种常染色体隐性遗传性疾病，以视网膜色素变性和听力损失为特征。USH 2型（USH 2）是USH最常见的类型，通常由USH 2A突变引起。在最近对日本USH 2患者进行USH 2A突变筛查中，我们在10名患者中发现了11种新突变，并发现了可能的频繁突变c。8559-2A>G在10名患者中的4名中。为了获得更精确的突变谱，我们在本研究中进一步分析了9例日本患者。我们发现了9个突变，其中8个是新的。这一结果表明，日本患者中USH 2A的突变谱与高加索人、犹太人和巴勒斯坦患者有很大不同。但我们没有找到C。8559-2A>G在本研究中。单倍型分析。8559-2G（突变）等位基因使用23个单核苷酸多态性周围的突变揭示了相同的单倍型模式，至少635 kb的长度，强烈表明突变起源于一个共同的祖先。事实上，所有携带C。8559-2A>G来自日本西部，表明该突变主要分布在该地区;事实上，本研究涉及的大多数患者来自日本东部，这导致了c的缺失。8559-2A>G. Journal of Human Genetics（2011）56，484-490; doi：10.1038/jhg.2011.45; 2011年5月19日在线发表
Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss. USH type 2 (USH2) is the most common type of USH and is frequently caused by mutations in USH2A. In a recent mutation screening of USH2A in Japanese USH2 patients, we identified 11 novel mutations in 10 patients and found the possible frequent mutation c. 8559-2A>G in 4 of 10 patients. To obtain a more precise mutation spectrum, we analyzed further nine Japanese patients in this study. We identified nine mutations, of which eight were novel. This result indicates that the mutation spectrum for USH2A among Japanese patients largely differs from Caucasian, Jewish and Palestinian patients. Meanwhile, we did not find the c. 8559-2A>G in this study. Haplotype analysis of the c. 8559-2G (mutated) alleles using 23 single nucleotide polymorphisms surrounding the mutation revealed an identical haplotype pattern of at least 635 kb in length, strongly suggesting that the mutation originated from a common ancestor. The fact that all patients carrying c. 8559-2A>G came from western Japan suggests that the mutation is mainly distributed in that area; indeed, most of the patients involved in this study came from eastern Japan, which contributed to the absence of c. 8559-2A>G. Journal of Human Genetics (2011) 56, 484-490; doi: 10.1038/jhg.2011.45; published online 19 May 2011