The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients
The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients
复制标题
DOI：
10.1038/jhg.2014.65
复制
发表时间：
2014-07
影响因子：
3.5
通讯作者：
Yang Zhao;Katsuhiro Hosono;Kimiko Suto;Chie Ishigami;Y. Arai;Akiko Hikoya;Y. Hirami;M. Ohtsubo;S. Ueno;H. Terasaki;Miho Sato;H. Nakanishi;S. Endo;K. Mizuta;H. Mineta;M. Kondo;Masayo Takahashi;S. Minoshima;Y. Hotta
中科院分区：
文献类型：
--
作者：
Yang Zhao;Katsuhiro Hosono;Kimiko Suto;Chie Ishigami;Y. Arai;Akiko Hikoya;Y. Hirami;M. Ohtsubo;S. Ueno;H. Terasaki;Miho Sato;H. Nakanishi;S. Endo;K. Mizuta;H. Mineta;M. Kondo;Masayo Takahashi;S. Minoshima;Y. Hotta
视网膜色素变性(RP)是一种高度异质性的遗传病。USH2A基因约占Usher综合征2型(USH2)病例的74-90%，也是高加索人群中常染色体隐性遗传相关基因(Arrp)的主要致病基因之一。为了确定日本RP患者中导致疾病的USH2A基因突变，通过直接测序对所有73个外显子进行了突变筛查。总共确定了100名没有全身症状的无血缘关系的日本RP患者，排除了具有明显常染色体显性遗传的家族。在这100名患者中，排除了18名极有可能具有致病EYS(闭眼同源)突变的RP患者后，82名纳入本研究。USH2A的突变分析在4名患者中发现了5个非常可能的致病突变。一名患者只有一个非常可能的致病突变，而其他患者有两个。未发现arrp中的p.C759f和USH2中的p.E767fs的高加索人频繁突变。4例患者均有典型的RP临床特征。在日本arrp患者中观察到的USH2A基因突变的发生率约为4%，并且USH2A基因突变在日本患者和以前报道的高加索人群中的分布有很大不同。
Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease. The USH2A gene, which accounts for approximately 74–90% of Usher syndrome type 2 (USH2) cases, is also one of the major autosomal recessive RP (arRP) causative genes among Caucasian populations. To identify disease-causing USH2A gene mutations in Japanese RP patients, all 73 exons were screened for mutations by direct sequencing. In total, 100 unrelated Japanese RP patients with no systemic manifestations were identified, excluding families with obvious autosomal dominant inheritance. Of these 100 patients, 82 were included in this present study after 18 RP patients with very likely pathogenic EYS (eyes shut homolog) mutations were excluded. The mutation analysis of the USH2A revealed five very likely pathogenic mutations in four patients. A patient had only one very likely pathogenic mutation and the others had two of them. Caucasian frequent mutations p. C759F in arRP and p. E767fs in USH2 were not found. All the four patients exhibited typical clinical features of RP. The observed prevalence of USH2A gene mutations was approximately 4% among Japanese arRP patients, and the profile of the USH2A gene mutations differed largely between Japanese patients and previously reported Caucasian populations.