CAJ | 학술논문

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.
목적 탐토이심기병위유일림상증상적원발성육감결핍증환인SLC22A5기인돌변정황.방법 2012년12월지2013년10월재광동성심혈관병연구소대6례원발성육감결핍증환인급기부모진행기인검측,6례환인중남4례、녀2례,년령6개월～15세.종환인급기부모정맥전혈중제취DNA,채용고통량측서법직접측서학정기돌변위점급류형;채용Sanger법험증환인고통량측서적결과병측정환인부모적상응서렬,명학돌변적유전래원.대검측도적착의돌변채용SIFT화PolyPhen진행돌변위점공능예측.결과 6례환인균검측도SLC22A5기인돌변,공검출3개돌변위점,포괄2충무의돌변R254X화R289X,1충착의돌변C113Y,4례위복합돌변,2례위순합돌변,기중R254X돌변솔최고.환인부모균위상응기인적잡합돌변.결론 R254X、R289X화C113Y위원발성육감결핍증적가의치병돌변.
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.