论文部分内容阅读
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。
Objective To investigate whether connexin26 (Cx26) gene is a nuclear modified gene of maternal hereditary deafness family with A1555G mutation in Huaiyin, Jiangsu Province. Methods The PCR restriction fragment length polymorphism (PCR-RFLP) and sequencing were used to analyze the genetic relationship between 26 maternal members and 62 controls in Huaiyin A1555G mutation-related maternal hereditary non-syndromic deafness (Including 2 paternal relatives, 10 mate controls and 50 local unrelated controls). The haplotype map of Cx26 gene was constructed based on Mendelian inheritance. Results Four heterozygous base changes were found in 26 maternal families, 79G → A, 109G → A, 341G → A and 235delC respectively. Among them, the first three are known polymorphisms, whereas 235delC is a known causative mutation that causes autosomal recessive deafness. However, the 235delC mutation is present only in one maternal family with a moderate deafness phenotype and in two of the children with normal hearing and does not co-segregate with deafness phenotypes. According to the law of inheritance, it is speculated that the mutation originated from one spouse control and was an extraneous mutation. Meanwhile, the Cx26 gene haplotypic map constructed according to four loci changes did not reveal any correlation between Cx26 gene and A1555G mutation deafness. In addition, one of the 235delC heterozygous deletion mutations was also found in 62 controls. Conclusion Heterozygous mutation of 235delC does not aggravate the deafness effect of A1555G mutation. Cx26 gene is also not a nuclear modified gene of A1555G mutation in Jiangsu Huaiyin maternal hereditary deafness family.