CX26基因在非综合征型耳聋中的产前诊断及早期干预

The prenatal diagnosis and early intervention of nonsyndromic hearing loss of connexin26 gene

目的：对非综合征型耳聋家系进行CX26基因的突变检测，对检测出CX26基因突变的家系进行产前诊断并实施早期干预。方法：对来自国内十多个省份的100个非综合征型耳聋家系中的先证者通过聚合酶链反应、单链构像多态性分析以及直接测序法进行CX26基因的突变检测，对确诊为CX26基因所致的遗传性耳聋家系中的一成员在妊娠时通过脐静脉穿刺术抽取脐胎血进行产前诊断及早期干预。结果：①发现CX26基因的致病性突变1种：cDNA编码区233～235位点c的纯合缺失；多态6种：G79A、G109A、A341G、G442A、G506A和T608C；②对一个确诊为CX26基因233~235delC的遗传性聋家系的成员于第2次妊娠时进行产前诊断，发现胎儿具有同种致病性突变。结论：①CX26基因cDNA编码区233～235位点C的杂合缺失不致聋，纯合缺失可导致非综合征型常染色体隐性遗传性聋；②产前诊断和早期干预可预防遗传性聋。这是我国首次确诊携带耳聋致病基因的胎儿并实施早期干预。

Objective：To detect the mutations of gene connexin26 in the pedigrees of nonsyndromic hearing loss, and to make prenatal diagnosis and carry out early intervention to the pedigrees with mutations of gene connexin26. Method：The connexin26 gene of probands in 100 nonsyndromic hearing loss pedigrees was inspected by polymerase chain reaction,single strand conformational polymorphism and direct sequencing to detect the gene mutations. To the pregnant women inpedigrees with confirmed nosogenetic mutations of connexin26 gene, the prenatal diagnosis to the fetus by condocentesis was made and the early intervention was carried out. Result：The homozygous deletion C at position 233-235 of connexin26 cDNA was proved to be a nosogenetic mutation, and G79A, G109A,A341G,G442A,GS06A and T608C were proved to be polymorphisms. In the prenatal diagnosis for the second pregnancy of a woman in a pedigree with the homozygous deletion C at position 233 - 235 of connexin26 eDNA, the same mutation in the fetus＇ connexin26 gene was found and she was advised to end the pregnancy. Conclusion：The homozygous deletion C at position 233- 235 of connexin26 eDNA will induce autosomal recessive nonsyndromic hereditary hearing loss and the heterogeneous mutation will not cause hearing loss. The prenatal diagnosis and early intervention can prevent the birth of deaf children. This is the first time in our country to make prenatal diagnosis and proceed early intervention to the fetus of hereditary hearing loss.