【摘要】 目的探讨连接蛋白26(connexin26,Cx26)基因是否是江苏淮阴A1555G突变相关母系遗传聋家系的核修饰基因。方法采用聚合酶链反应限制片断长度多态性分析(PCR restriction fragmentlength polymorphism,PCRRFLP)和测序技术,对江苏淮阴A1555G突变相关母系遗传非综合征型聋核心家系中的26例母系成员和62例对照(包括2例父系亲属、10例配偶对照和50例当地无关对照)的Cx26基因编码区序列进行了研究,并根据孟德尔遗传规律构建了家系成员Cx26基因的单体型图。结果在26例母系成员中共发现4处杂合性碱基变化,分别为79G→A、109G→A、341G→A和235delC。其中,前3种为已知多态性差异,而235delC为已知的可引起常染色体隐性聋的致病突变。但235delC突变仅存在于1例具有中度聋表型的母系成员和其2例听力正常的子女中,并不与耳聋表型共分离。而根据遗传规律,推测该突变来源于1例配偶对照,为外来突变;同时,根据4个位点变化构建的Cx26基因单体型图也未揭示Cx26基因与A1555G突变致聋有任何相关性;另外,在62例对照中也发现1例235delC杂合性缺失突变。结论235delC杂合性突变并不加重A1555G突变的致聋效应;Cx26基因也不是江苏淮阴母系遗传聋家系A1555G突变的核修饰基因。更多还原

【Abstract】 Objective To ascertain whether connexin 26 (Cx26) gene was a nuclear modifier gene in an extensive family with matrilineal nonsyndromic deafness associated with A1555G mutation in Huaiyin,China. Methods Following PCR-restriction fragment length polymorphism(PCR-RFLP) with ApaI restriction enzyme, Cx26 genes from 26 cases, with A1555G mitochondrial mutations in this family, and 62 controls (including 2 patrilineal relatives, 10 spouse controls and 50 unrelated controls), were sequenced. Results Compared with the reference sequence of Cx26 gene, totally four kinds of nucleotide changes,79G→A,109G→A,341G→A and 235delC,were detected in a heterozygous form. However, the former three were previously reported polymorphisms, and only the 235delC was a previously described recessive mutation associated with most autosomal nonsyndromic sensorineural hearing loss in Japan and China. Further study showed that the heterozygous 235delC mutation existed in both one individual with mild hearing loss and two individuals with normal hearing. Clinical characterization showed that 235delC mutation did not seem to modify the deafness phenotype due to the A1555G mutation. Moreover, this 235delC mutation was deduced to derive from a married-in control. Finally, there were no co-segregation between the phenotypes of hearing loss and the genotypes for Cx26 genes based on the four kinds of nucleotide changes. Conclusions The heterozygous 235delC mutation of the Cx26 gene may not modulate the severity of hearing loss associated with A1555G mutation and Cx26 gene is unlikely to be a modifier gene for hearing loss due to A1555G mitochondrial mutation in this Chinese family.更多还原