Duchenne型肌营养不良症家系的多重PCR和STR-PCR基因诊断  

Genediagnosis by multiplex PCR and STR- PCR for Duchenne muscular dystrophy families

作　　者：窦瑞艳 赵胜科 陈靖 郑天津 卢雪梅[1] 张凤立[1] 王超彦 李红智[1] 

机构地区：[1]温州医科大学生命科学学院浙江省医学遗传学重点实验室,温州325035 [2]温州市人口和计划生育委员会,温州325000 [3]温州市计划生育宣传技术指导站,温州325000

出　　处：《中国优生与遗传杂志》2014年第2期10-12,91,F0002,F0003,共6页Chinese Journal of Birth Health & Heredity

基　　金：浙江省人口和计划生育科技项目(201107);温州医学院横向科研项目(HX1202)

摘　　要：目的该研究率先开展温州地区Duchenne型肌营养不良症(DMD)家系的缺失基因诊断特别是STR单体型连锁基因诊断,为基于DMD症状前、携带者基因诊断结果的遗传咨询和生育指导提供依据。方法针对4例DMD先证者,采用多重PCR检测常见18个外显子缺失,进行直接基因诊断。针对未能发现常见外显子缺失的DMD先证者及其有关家系成员,采用短串联重复序列(STR)PCR检测5个位点(3’CA、44CA、45CA、49CA和50CA)STR多态性,进行间接单体型连锁基因诊断。结果家系二的先证者缺失外显子3、4和6。其余3个家系的先证者的异常X染色体均肯定来源于其母亲。家系一先证者外婆肯定是携带者。家系三先证者年幼(4周岁)弟弟肯定为正常人,将来年龄大了也不会发病,先证者外婆肯定是携带者。家系四先证者刚出生的妹妹肯定是遗传携带者,将来其生育儿子有遗传患病风险。结论该研究的DMD家系的缺失和STR单体型连锁基因诊断,特别是对症状前男孩的诊断、对无患病后代的女性携带者的检出,具有非常重要的实际意义,可以为遗传咨询和生育指导提供可靠依据。Objective： To develop deletion gene diagnosis and STR heplotype linkage gene diagnosis for Duchenne muscular dys- trophy （DMD） pedigrees in Wenzhou, further to provide evidences for genetic counseling and family planning guidance according to the gene prognosis results of males and female carriers for DMD. Methods： For detecting frequent deletions for 4 cases of DMD proband, multiplex polymerase chain reaction （PCR） was used to detect deletions in 18 exons of dystrophin gene, processing direct gene diagnosis. For the pedigrees with no deletion found, short tandem repeat （STR） - PCR was used to analyze the STR polymor- phism in five sites （3＇ CA, 44CA, 45CA, 49CA and 50CA） of dystrophin gene, processing indirect haplotype linkage gene diagno- sis. Results： The deletions in exon 3, 4 and 6 were found in the proband of pedigree 2. In other three pedigrees, the abnormal X chromosome of proband was inherited from his mother respectively. The grandmother of proband in pedigree 1 is carrier. In pedigree 3, the very little （4 - year old） brother of proband is normal and will be normal even getting elder, the grandmother of proband is carrier. The just - born little sister of proband is heredity carrier in pedigree 4, and for her sons there will be heredity risk. Conclusion ： The deletion and STR haplotype linkage gene diagnosis of DMD pedigrees of this study, especially the presymptomatic gene diagnosis of males, the gene diagnosis of female carriers without DMD offspring, would have their very important clinical implications, could pro- vide reliable evidences for genetic counseling and family planning guidance.

关 键 词：Duchenne型肌营养不良症(DMD) 基因诊断 多重PCR STR多态性 单体型连锁分析 

分 类 号：R746.2[医药卫生—神经病学与精神病学]