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目的探讨线粒体m.1555A>G突变致聋家系临床表型异质性的遗传学基础。方法收集9个线粒体m.1555A>G突变致聋大家系的临床资料及外周血样本,运用PCR产物直接测序技术对家系耳聋患者进行GJB2、GJB3、SLC26A4基因、线粒体m.1494C>T、m.7445A>G、D-loop区及部分单倍型划分标志性位点检测分析,划分上述致聋家系的线粒体单倍型。结果9个家系共检出A、B、D、F、G、M7等6种线粒体单倍型,共耳聋患者25例,家系母系成员耳聋外显率为12.5%~50.0%(平均外显率31.3%,25/80),除家系4先证者复合存在GJB2基因c.235del C杂合突变,其余先证者均未检出其他相关突变。结论单倍型B的m.1555A>G突变耳聋家系具有高致聋外显率46.2%(12/26),GJB2、GJB3、SLC26A4等核基因及m.1494C>T、m.7445A>G等相关致聋位点非本研究耳聋家系的临床表型相关修饰位点。
Objective To investigate the genetic basis of the clinical phenotypic heterogeneity in the deafness-dependent families with mitochondrial m.1555A> G mutation. Methods The clinical data and peripheral blood samples from 9 families with deafness caused by mitochondrial m1555A> G mutation were collected and the GJB2, GJB3 and SLC26A4 genes and mitochondria m.1494C> T, m were detected in the family deafness patients by PCR sequencing. 7445A> G, D-loop region and part of the haplotype marker site detection and analysis, delineation of the deafness of the family of mitochondrial haplotype. Results A total of 6 mitochondrial haplotypes (A, B, D, F, G, M7) were detected in 9 pedigrees with 25 cases of deafness. The penetrance of deafness in family members was 12.5% ~ 50.0% (mean penetrance 31.3%, 25/80). Except for the family 4 probands, there was a heterozygous mutation of c.235del C in GJB2 gene. No other related mutations were detected in the remaining probands. Conclusion The haplotype B m 1.55 A> G mutation deafness pedigree has high deafness penetrance 46.2% (12/26), GJB2, GJB3, SLC26A4 and other nuclear genes and m.1494C> T, m.7445A> G The relevant deafness sites are not related to the clinical phenotype-related modification sites of the deafness pedigrees in this study.