一个中国Usher综合征2型家系中USH2A基因的2个新的致病突变

Mutation screening of the USH2A gene reveals two novel pathogenic variants related to simplex Usher syndrome 2 in Chinese patients

目的为了扩大USH2A突变的范围并进一步揭示USH2A基因在2型Usher综合征(Usher syndrome type 2, USH2)中的作用,对中国的USH2患者进行了USH2A基因突变筛选。方法从收集到的中国USH2患者及其家属的外周血中提取基因组DNA,设计特异性引物扩增USH2A基因编码区(外显子2-72)并使用Sanger测序研究等位基因并与NCBI数据库中的标准序列进行比对。使用PolyPhen-2等预测软件对筛选出来的突变的致病性进行预测。结果在1例患者中检测到2个之前未报道过的致病的杂合突变c.230dupA(Phe78Valfs*30)和c.4085C>T(p.Pro1362Leu)。结论通过全外显子测序鉴定了可能导致USH2的2个新的杂合USH2A基因致病突变。这一结果扩大了已知的USH2A基因致病突变的范围。

Objective To investigate mutations of USH2A gene in Chinese patients with Usher syndrome type 2(USH2).Methods Genomic DNA was extracted from the peripheral blood of unrelated 8 Chinese USH2 patients and their parents.The specific primers for amplifying the coding region(exons 2-72)of the USH2A gene were designed.Sanger sequencing was used to study alleles.Silico prediction tools such as PolyPhen-2 were used to predict the pathogenicity of the variants identified in these patients.Results Two novel heterozygous pathogenic variants c.230dupA(Phe78Valfs*30)and c.4085C>T(p.Pro1362Leu)were detected in a patient.Conclusion We identified two novel heterozygous pathogenic variants in the USH2A gene that might cause the USH2.It expands the spectrum of USH2A variants in USH.