MYO15A基因突变致聋家系的遗传学分析

Genetic analysis for hearing Loss pedigree with MYO15A gene mutation

目的对一常染色体隐性遗传性耳聋家系行遗传学分析及产前诊断。方法收集该家系成员的临床资料及外周血血样,运用十五项遗传性耳聋微阵列芯片及二代测序技术对先证者进行基因组全外显子序列分析,对检出的致病突变进行Sanger测序验证,结合应用STR检测技术对该家系行产前分子诊断。结果该家系先证者为极重度感音神经性耳聋患者,存在MYO15A基因c.9400C>T(p.R3134X)纯合突变,父母亲均为c.9400C>T(p.R3134X)杂合突变携带者,孕母亲产前诊断结果提示胎儿该位点基因型与先证者相同。结论 MYO15A基因c.9400C>T(p.R3134X)突变为该家系耳聋患者的致聋遗传因素;二代测序结合Sanger测序法有助于明确耳聋患者热点基因突变以外的罕见致聋基因及其位点。

Objective：To conduct genetic analysis and attempt prenatal molecular diagnosis in a Chinese family with autosomal recessive inheritance hearing loss. Methods：Blood samples and clinical data of all members from the family were collected.The mutation was identified by fifteen Deafness-Related Gene Mutations Detection kit（microarray）and Nextgeneration sequencing,and then was confirmed by Sanger sequencing. Maternal DNA contamination was excluded by application of STR detecting in the process of prenatal molecular diagnosis. Results：Homozygous mutation of c.9400 C〉T（p.R3134 X）in MYO15A gene was detected in the patient who presented profound sensorineural hearing loss,whose parents were found to carry heterozygous mutation of c.9400 C〉T（p.R3134 X）. Prenatal diagnostic testing showed that the fetus shares the same genotype in MYO15A gene with proband. Conclusion：Homozygous mutation of c.9400 C〉T（p.R3134 X）in MYO15A gene were elucidated to be the molecular basis of the proband with hearing impairment.Next-generation sequencing combined with Sanger sequencing was contributes to identify the rare deafness genes and mutations in the patient with deafness.