CFTR基因5T纯合突变导致先天性双侧输精管缺如一例家系报道  

Homozygous 5T alleles, clinical presentation and genetic analysis within a family with congenital bilateral absence of the vas deferens

作　　者：冯嘉荣 张亚男[1] 吴晓 杨晓健[1] 陈石涛 马功朝 罗少戈 张炎[1] Feng Jiarong , Zhang Yanan, Wu Xiao, Yang Xiaojian, Chen Shitao, Ma Gongchao, Luo Shaoge, Zhang Yan.(Department of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Chin)

机构地区：[1]中山大学附属第三医院不育与性医学科,广州510630 [2]中山大学孙逸仙纪念医院泌尿外科 [3]中国福利会国际和平妇幼保健院泌尿男科

出　　处：《中华医学杂志》2018年第18期1414-1418,共5页National Medical Journal of China

基　　金：国家自然科学基金（81571424,81771565）;广东省自然科学基金（2014A030313045）

摘　　要：目的研究一个国内先天性双侧输精管缺如患病家系的囊性纤维化跨膜转导调节（CFTR）基因的突变基因型及遗传特征。方法门诊收录因无精子症所致的不育症来就诊的两兄弟（33岁／29岁），根据阴囊触诊、精液常规检查、阴囊及经直肠超声检查等诊断为先天性双侧输精管缺如，抽取该家系患者及双亲共4人的外周血样本，用试剂盒提取白细胞基因组，PCR法扩增CFTR基因上27个外显子及其侧翼序列并行Sanger测序，结果在美国国立生物技术信息中心（NCBI）数据库在线比对。结果基因测序筛查排除CFTR基因外显子区域无致病或可疑突变后，综合双向测序结果，在CFTR基因10号外显子前的剪切位点上的多T序列中发现患有先天性双侧输精管缺如的两兄弟相同的纯合5T突变（13TG-5T／12TG-5T），2条5T等位基因分别源于父亲（12TG-5T／12TG-7T）和母亲（13TG-5T／11TG-7T）；家系图谱分析提示5T纯合突变与先天性双侧输精管缺如发病相关，带纯合5T等位基因的患者将致病基因传给后代的危险度约是正常人群的20倍。结论CFTR基因上的5T突变是该患病家系中可遗传的致病基因位点，5T纯合突变可导致先天性双侧输精管缺如。从遗传咨询角度考虑，建议患病夫妻双方均行CFTR基因筛查并考虑胚胎植入前遗传学诊断。Objective To study the cystic fibrosis transmembrane regulator（CFTR） genotypes and genetic characteristics of a Chinese family with Congenital bilateral absence of vas deferens （CBAVD）. Methods Two 33/29-years-old brothers presented with CBAVD-caused obstructive azoospermia were diagnosed on the basis of scrotal palpation, analysis of semen and ultrasound tests. We extracted their genomic DNA as well as their healthy parents＇ from the peripheral blood leukoeytes. To identify CFTR mutations, each of the 27 exons of the CFTR gene and their flanking splice sites sequences were amplified by polymerase chain reaction （PCR） and subsequently studied with Sanger sequencing. Mutations/variations were identified and compared with the control sequence searched in the NCBI database. Results Homozygous 5T mutation at the splicing site ahead of exon 10 of the CFTR gene was identified in both brothers in association with 13TG and 12TG alleles（13TG-ST/12TG-ST）, one of those was inherited from the mother （ 13TG-ST/11TG-7T）, the other was from the father （12TG-ST/12TG-7T）. All of the results above had been excluded the presence of other mutations. Genetic study of this family supports that homozygous 5T mutation is associated with CBAVD. Individuals with homozygous 5T alleles are 20 times more possible to transmit this deleterious variant to the next generation than general population. Conclusions This family we analysed agrees with the previous conclusion that 5T allele is a deleterious and heritable mutation which could cause CBAVD. Considering better genetic counseling, CFTR gene detection and Preimplantation genetic diagnosis （PGD） are suggested for CBAVD couples who seek for reproductive assistance.

关 键 词：泌尿生殖系统畸形 先天性双侧输精管缺如 无精子症 囊性纤维化跨膜传导调节因子 突变 基因测定 遗传咨询 

分 类 号：R698.2[医药卫生—泌尿科学]