Comprehensive Molecular Screening in Chinese Usher Syndrome Patients
Comprehensive Molecular Screening in Chinese Usher Syndrome Patients
复制标题
中国亚瑟综合症患者的综合分子筛查
DOI：
10.1167/iovs.17-23312
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发表时间：
2018-03-01
影响因子：
4.4
通讯作者：
Li, Yang
中科院分区：
文献类型：
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作者：
Sun, Tengyang;Xu, Ke;Li, Yang
目的. Usher综合征（USH）是一组常染色体隐性遗传性疾病，可引起耳聋和失明。本研究的目的是确定中国人群USH患者的突变谱，并描述突变患者的临床特征。共招募了119名临床诊断为USH的先证者进行遗传分析。所有先证者均接受眼科检查。使用分子筛选方法的组合，包括靶向下一代测序、Sanger-DNA测序和多重连接探针扩增测定来检测突变。我们发现92例先证者（77.3%）有双等位基因突变，5例患者（4.2%）有单等位基因突变，1例患者（0.8%）有1个半合子模仿，导致总体突变检出率为78.2%。总的来说，132个不同的致病突变涉及7个USH（ABHD 12，CDH 23，GPR 98，1111- 07 A，PCDH 15，11，SH 1C和. USH 2A）基因; 5个其他视网膜变性基因（CHM，CIVGA 1，EYS，PDE 613和TULP 1）和1个非综合征性听力损失基因（MY 0/5A）被确定，78个是新的。MY 0A 7突变导致60%的USH 1家族，其次是PCDH 15（20%）和USHIC（10%）。115：112 A突变占USII 2家系的67.7%，其中以c.8559-2A>6突变最常见，占GS/12 A等位基因的19.1%。我们的研究结果证实，中国患者的USH基因突变谱与其他人群不同。中国人群突变谱的形成将使未来对USH患者进行精确的基因诊断成为可能。
PURPOSE. Usher syndrome (USH) refers to a group of autosomal recessive disorders causing deafness and blindness. Th.e objectives of this study were to determine the mutation spectrum in a cohort of Chinese patients with USH and to describe the clinical features of the patients with mutations.METHODS. A total of 119 probands who were clinically diagnosed with USH were recruited for genetic analysis. All probands underwent ophthalmic examinations. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger-DNA sequencing, and multiplex ligation probe amplification assay, was used to detect mutations.RESULTS. We found biallelic mutations in 92 probands (77.3%), monoallelic mutations in 5 patients (4.2%), and 1 hemizygous imitation in 1 patient (0,8%), resulting in an overall mutation detection rate of 78.2%. Overall, 132 distinct disease-causing mutations involving seven USH (ABHD12, CDH23, GPR98,1111-07A, PCDH15, 11,SH1C, and. USH2A) genes; 5 other retinal degeneration genes (CHM, CIVGA 1, EYS, PDE613, and TULP1); and 1 nonsyndromic hearing loss gene (MY0/5A) were identified, and 78 were novel. Mutations of MY0A 7 were responsible for 60% of USH1 families, followed by PCDH15 (20%) and USHIC (10%). Mutations of 115:112A accounted for 67.7% of USII2 families, and mutation c.8559-2A>6 was the most frequent one, accounting for 19.1% of the identified GS/12A alleles.CONCLUSIONS. Our results confirm that the mutation spectrum for each USH gene in Chinese patients differs from those of other populations. The formation of the mutation profile for the Chinese population will enable a precise genetic diagnosis for USH patients in the future.