两个遗传性耳聋家庭GJB2基因突变的鉴定及遗传性分析

Identified GJB2 gene mutation in two families with hereditary deafness and genetic analysis

目的高通量基因测序技术对两个遗传性耳聋家庭进行测序,探讨婚前基因筛查在耳聋患者中的应用。方法对先证者及家系成员进行病史采集、体格检查、听力学评估。获取外周血,提取基因组DNA,对406个耳聋基因进行检测,对突变位点Sanger测序验证分析。结果两个家系中先证者及他们的双亲均为耳聋患者,基因检测发现两个家系所有成员均为GJB2纯合/杂合致病突变。先证者1检出c.235delC/c.598G>A复合杂合突变,其父亲为c.235delC纯合突变,母亲为c.598G>A/c.299-300delAT复合杂合突变。先证者2检出c.235delC/c.299-300delAT符合杂合突变,其父亲为c.235delC/c.299-300delAT复合杂合突变,母亲为c.235delC纯合突变。结论孕前耳聋基因筛查应作为常规检测项目,并进行遗传咨询,指导婚育,避免耳聋患儿出生,尤其在夫妻双方均为耳聋患者的婚配家庭。

Objective To analyze the mutations of deafness genes in two children from different family by High-throughput sequencing,and to explore the application of premarital genetic screening in deafness patients.Methods Medical history collection,physical examination and audiological evaluation were performed on the two probands and their family members.Genomic DNA was extracted from peripheral blood of all individuals.406 genes associated with inherited hearing loss were sequenced by high-throughput sequencing,mutations detected in the probands and their parents were verified by Sanger sequencing.Results The probands and their parents in the two families were deafness patients,and genetic testing revealed that the two families with GJB2 homozygous/heterozygous pathogenic mutations.proband 1 detected c.235delC/c.598G>A heterozygous mutation of GJB2,his father with c.235delC homozygous mutation,and his mother with c.598G>A/c.299-300delAT heterozygous mutation.Proband 2 detected c.235delC/c.299-300delAT heterozygous mutation,his father with heterozygous mutation of c.235delC/c.299-300delAT,and his mother with c.235delC homozygous mutation.Conclusion It is recommended that deafness patients get gene sequencing before marriage,conduct genetic counseling,guide marriage and childbirth,and avoid the deafness children birth.Especially both husband and wife are deaf.