杜氏/贝氏肌营养不良症4个家系的直接和间接连锁基因诊断分析

Direct and indirect linkage gene diagnosis and analysis for Duchenne/Becker muscular dystrophy families

目的:开展温州地区杜氏/贝氏肌营养不良症(DMD/BMD)4个家系的直接和间接连锁基因诊断,进一步为基于DMD/BMD症状前男性患者和女性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/BMD先证者,采用多重PCR技术检测常见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/BMD先证者及其有关家系成员,采用短串联重复序列(STR)-PCR技术检测第50内含子STR多态性,进行连锁基因诊断。结果:家系2的先证者缺失外显子48、49。家系1中先证者二姨不是携带者。家系3中,儿子均正常的先证者大姨、三姨都是携带者,二姨未婚二女儿是携带者,先证者幼小弟弟为正常者,即使年龄增大也不会发病。家系4中刚出生的先证者妹妹是携带者。结论:本研究的DMD/BMD家系的直接和间接连锁基因诊断结果,特别是症状前男性患者诊断结果、尚无患儿的女性携带者的检出结果,具有一定的临床意义,可以为遗传咨询和生育指导提供可靠依据。

Objective： To develop direct and indirect linkage gene diagnosis for Duchenne/Becker musculardystrophy （DMD/BMD） pedigrees in Wenzhou, and to further provide evidences for genetic counseling and family planning guidance according to the gene prognostic results of males and the gene diagnostic results of female carriers for DMD/BMD. Methods： For detecting frequent deletions for 4 cases of DMD/BMD 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 polymorphism in intron 50 of dystrophin gene, processing indirect linkage gene diagnosis. Results： The deletions in exon 48, 49 were found in the proband of pedigree 2. The 2nd aunt of proband in pedigree 1 is not carrier. In pedigree 3, the 1st and 3rd aunts of proband are carriers though their sons are all normal, the un-married daughter of 2nd aunt of proband is carrier, and the very little brother of proband is normal and will be normal even getting elder. The just-born little sister of proband is carrier in pedigree 4. Conclusion： The direct and indirect linkage gene diagnostic results of the DMD/BMD pedigrees, especially the gene prognostic results of males, the gene diagnosis results of female carriers without DMD/BMD son, will have their very important clinical implications, can provide reliable evidences for genetic counseling and family planning guidance.