原发性肉碱缺乏症性心肌病患儿基因突变及家系分析

Genetics and pedigree analysis of primary carnitine deficiency cardiomyopathy in 6 cases

目的 探讨以心肌病为唯一临床症状的原发性肉碱缺乏症患儿SLC22A5基因突变情况.方法 2012年12月至2013年10月在广东省心血管病研究所对6例原发性肉碱缺乏症患儿及其父母进行基因检测,6例患儿中男4例、女2例,年龄6个月～15岁.从患儿及其父母静脉全血中提取DNA,采用高通量测序法直接测序确定其突变位点及类型;采用Sanger法验证患儿高通量测序的结果并测定患儿父母的相应序列,明确突变的遗传来源.对检测到的错义突变采用SIFT和PolyPhen进行突变位点功能预测.结果 6例患儿均检测到SLC22A5基因突变,共检出3个突变位点,包括2种无义突变R254X和R289X,1种错义突变C113Y,4例为复合突变,2例为纯合突变,其中R254X突变率最高.患儿父母均为相应基因的杂合突变.结论 R254X、R289X和C113Y为原发性肉碱缺乏症的可疑致病突变.

Objective To investigate the mutation and background of SLC22A5 in 6 patients with primary carnitine deficiency （PCD） who only presented as cardiomyopathy.Method Genomic DNA were abstracted from the blood of the patients and their parents.Using high-throughput sequencing to determine the mutation site.Using Sanger method to confirm the mutated alleles in PCD patients and detect the corresponding sequences in their patients.Using SIFT and PolyPhen to predict the function of protein for detected missense mutations.Result Three different mutations were identified,including 2 nonsense mutations （R254X and R289X）,1 missense mutation （C113Y）,R254X was the most frequently seen mutation.Four patients had compound heterozygous mutations and 2 patients had homozygous mutations.Their parents were found to have heterozygous mutations in corresponding alleles.Conclusion R254X,R289X and C113Y might be associated with primary carnitine deficiency.