PDF(Pubmed)
Abstract：
Purposes: We aimed to characterize the USH2A genotypic spectrum in a Chinese cohort and provide a detailed genetic profile for Chinese patients with USH2A-IRD. Methods: We designed a retrospective study wherein a total of 1,334 patients diagnosed with IRD were included as a study cohort, namely 1,278 RP and 56 USH patients, as well as other types of IEDs patients and healthy family members as a control cohort. The genotype-phenotype correlation of all participants with USH2A variant was evaluated. Results: Etiological mutations in USH2A, the most common cause of RP and USH, were found in 16.34% (n = 218) genetically solved IRD patients, with prevalences of 14.87% (190/1,278) and 50% (28/56). After bioinformatics and QC processing, 768 distinct USH2A variants were detected in all participants, including 136 disease-causing mutations present in 665 alleles, distributed in 5.81% of all participants. Of these 136 mutations, 43 were novel, nine were founder mutations, and two hot spot mutations with allele count ≥10. Furthermore, 38.5% (84/218) of genetically solved USH2A-IRD patients were caused by at least one of both c.2802T>G and c.8559-2 A>G mutations, and 36.9% and 69.6% of the alleles in the RP and USH groups were truncating, respectively. Conclusion: USH2A-related East Asian-specific founder and hot spot mutations were the major causes for Chinese RP and USH patients. Our study systematically delineated the genotype spectrum of USH2A-IRD, enabled accurate genetic diagnosis, and provided East Asian and other ethnicities with baseline data of a Chinese origin, which would better serve genetic counseling and therapeutic targets selection.
摘要：
目的：我们旨在表征中国人群的USH2A基因型谱，并为中国USH2A-IRD患者提供详细的遗传图谱。方法：我们设计了一项回顾性研究，共纳入1,334例确诊为IRD的患者作为研究队列，即1278名RP和56名USH患者，以及其他类型的IED患者和健康家庭成员作为对照队列。评估了所有具有USH2A变体的参与者的基因型-表型相关性。结果：USH2A的病因突变，RP和USH的最常见原因，在16.34%(n=218)基因解决的IRD患者中发现，患病率为14.87%（190/1,278）和50%（28/56）。经过生物信息学和QC处理，在所有参与者中检测到768种不同的USH2A变体，包括665个等位基因中存在的136个致病突变，分布在所有参与者的5.81%中。在这136个突变中,43是小说，九个是创始人突变，和两个等位基因计数≥10的热点突变。此外，38.5％（84/218）的遗传解决的USH2A-IRD患者是由c.2802T>G和c.8559-2A>G突变中的至少一个引起的，RP和USH组中36.9%和69.6%的等位基因截短，分别。结论：与USH2A相关的东亚特异性创始人和热点突变是中国RP和USH患者的主要原因。我们的研究系统地描绘了USH2A-IRD的基因型谱，能够进行准确的基因诊断，并为东亚和其他种族提供了中国血统的基线数据，这将更好地服务于遗传咨询和治疗目标的选择。
