摘要： 目的 针对先天性耳聋家系进行致病基因突变鉴定及产前诊断。方法 应用目标基因捕获和高通量测序技术（panel）对先证者进行耳聋相关基因全外显子和相邻内含子测序筛选致病基因；应用Sanger测序和生物信息学分析对致病突变做家系验证，并针对此突变进行产前诊断。结果 先证者携带PCDH15基因第27号外显子c.3490_3491insA（p.M1164Nfs*12）和第31号外显子c.4115delG（p.G1372Efs*4）复合杂合突变，分别来源于父亲和母亲。这两种移码突变未见数据库和文献收录，均导致蛋白质翻译提前终止，形成截短蛋白，根据ACMG解读规则预测为致病性突变。产前诊断结果显示，胎儿携带与先证者相同的复合杂合突变。结论 确诊Usher综合征1型家系，发现PCDH15基因2个新的致病突变位点c.4115delG和c.3490_3491insA，该复合杂合突变是此家系致病的分子基础，丰富了PCDH15基因的突变谱。

Usher综合征1型家系PCDH15基因的突变分析与产前诊断

李亚娟^1,2, 孟繁杰², 罗丽双², 于月新², 郝冬梅²

1. 锦州医科大学北部战区总医院研究生培养基地, 沈阳 110016;
2. 北部战区总医院生殖医学科, 沈阳 110016

收稿日期:2019-03-26出版日期:2020-03-30发布日期:2020-03-19
通讯作者:郝冬梅E-mail:1260553806@qq.com
作者简介:李亚娟(1980-),女,主治医师,硕士研究生.
基金资助:辽宁省自然科学基金（20180551228）


关键词: PCDH15基因, Usher综合征, 耳聋, 高通量测序
Abstract: Objective To identify the causative gene and locus of a congenital deafness pedigree and subsequently carry out a prenatal diagnosis. Methods Next-generation sequencing (NGS) technology was used to analyze deafness-related genes by capturing the whole exons and adjacent intronic regions. Suspected mutations were verified by Sanger sequencing. Based on the positive results obtained from the genetic testing,a prenatal diagnosis of the fetus was performed. Results The proband was detected to carry compound heterozygous mutations in the protocadherin related 15 (PCDH15) gene,c.3490_3491insA (p.M1164Nfs*12) of exon 27,and c.4115delG (p.G1372Efs*4) of exon 31 on chromosome 10. The c.3490_3491insA frameshift mutation originated from the father,while the c.4115delG mutation was derived from the mother,which led to the early termination of protein translation. c.4115delG and c.3490_3491insA were identified as novel mutations,predicted to be pathogenic according to the ACMG guidelines. In addition,the prenatal diagnosis showed that the fetus carried the same compound heterozygosity of PCDH15 as the proband. Conclusion The deafness phenotype of our patient may be attributed to compound heterozygous mutations of PCDH15 at loci c.3490_3491insA and c.4115delG. Identification of two novel mutations has enriched the mutational spectrum of the PCDH15 gene.
Key words: PCDH15, Usher syndrome, hearing loss, next-generation sequencing
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