罕见耳聋家系GJB2基因新发突变基因检测和产前基因诊断

Detection and prenatal diagnosis of GJB2 gene novel mutation in a rare Chinese family with hereditary hearing loss

目的对1个耳聋家系进行耳聋致病基因检测和胎儿产前诊断,探讨建立遗传性耳聋产前诊断规范流程。方法1个耳聋家系,采用耳聋基因芯片对先证者和家系成员进行遗传性耳聋基因突变初筛;采用PCR反应和Sanger测序进行GJB2基因编码区突变分析,采用羊膜穿刺术对胎儿进行突变位点分析。取50例听力正常的健康人DNA作为对照并对新生儿进行随访,检测新生儿听性脑干反应阈值。结果该家系中检测到已知致病性突变c.235del C和c.299del AT,新发突变c.446C>A(p.149Ala>Asp);在50例正常人的DNA中未检测到c.446C>A(p.149Ala>Asp)突变;排除羊水母体污染,检测到胎儿携带235del C杂合突变;新生儿听性脑干反应阈值:左耳25db,右耳30db,听力正常。结论突变c.446C>A(p.149Ala>Asp)可能是该家系中致病性突变,可能是GJB2基因的一种新致病性突变。

Objective To discuss the standard process of prenatal diagnosis by detecting the virulence gene and making prenatal molecular diagnosis in a family with hereditary hearing loss.Methods Gene chip of hearing loss was employed to detect the mutational hotspot.The whole coding region of GJB2 gene was analyzed by PCR and Sanger sequencing.The mutation of fetus was analyzed by amniocentesis.Fifty DNA samples from normal hearing people were detected as controls.The neonates were followed up and deteced the auditory brainstem response threshold.Results Two pathogenic frameshift mutations（c.235 del C and c.299 del AT）and a novel missense mutation（c.446C〉A,p.149Ala〉Asp）were identified.The novel mutation did not appear in GJB2 gene of normal control subjects.The fetus carried the c.235 del C mutation.The auditory brainstem response threshold was 25 db in the left ear and 36 db in the right ear,with normal hearing.Conclusion The novel mutation（c.446C〉A,p.149Ala〉Asp）is considered as a pathogenic mutation of this family and is also a novel pathogenic mutation of GJB2 gene.