下颌骨发育不良伴A型脂肪代谢障碍一家系报告  

A family study of mandibuloacral dysplasia with type A lipodystrophy

作　　者：向上[1,2] 张璇[2] 李雪怡[1,2] 毕杨[2] 肖农[1,2] 

机构地区：[1]重庆医科大学附属儿童医院康复科,重庆400014 [2]儿童发育疾病研究部共建教育部重点实验室儿科学重庆市重点实验室重庆市儿童发育重大疾病诊治与预防国际科技合作基地,重庆400014

出　　处：《临床儿科杂志》2014年第11期1084-1088,共5页Journal of Clinical Pediatrics

摘　　要：目的研究下颌骨发育不良伴A型脂肪代谢障碍(MADA)家系的基因突变情况和临床特征。方法以2例临床拟诊为早老症的兄妹及其家庭成员共5名为研究对象,并详细收集临床资料。提取家系成员外周血DNA进行聚合酶链反应(PCR)扩增,并直接测序。Blast在线软件比对分析以明确突变位点,并使用SIFT和Poly Phen-2分析突变位点的有害性。结果 2例患儿的临床特征符合MADA。该家系中存在LMNA基因第9号外显子c.1579C>T(p.Arg527Cys)和c.1583C>T(p.Thr528Met)的2个突变位点,父亲c.1583C>T(p.Thr528Met)、母亲c.1579C>T(p.Arg527Cys)及正常女儿c.1583C>T(p.Thr528Met)均为杂合突变携带者,而2例患儿为上述2个位点的双重杂合突变,为常染色体隐性遗传。SIFT和Poly Phen-2分析结果表明2个位点均对蛋白质功能有害。结论该家系2例MADA患儿为LMNA基因双重杂合突变致病。Objective To study the gene mutations and clinical features of mandibuloacral dysplasia with type A lipodystrophy （MADA） in a Chinese family. Methods The information of 5 family members including 2 siblings suspected atyp-ical progeria was assembled. Genomic DNA was extracted from peripheral blood of 5 family members, the 12 exons of LMNA gene were ampliifed by PCR and then the PCR products were directly sequenced and analyzed by using Blast software online. The SIFT and PolyPhen-2 software were used to predict the harmfulness of mutations. Results The 2 siblings were clinically diagnosed as MADA. Heterozygous c.1579C〉T （p.Arg527Cys） and c.1583C〉T （p.Thr528Met） mutations were detected in this family. The father carried c.1583C〉T （p.Thr528Met） mutation, the mother carried c.1579C〉T （p.Arg527Cys） mutation, and their normal daughter were all heterozygous carriers with c.1583C〉T （p.Thr528Met） mutation. Compound heterozygous c.1579C〉T （p.Arg527Cys） and c.1583C〉T （p.Thr528Met） mutations in 2 siblings led to MADA. The MADA showed an autosomal re-cessive inheritance pattern in this family. Conclusions The 2 siblings with MADA in this family were caused by compound heterozygous mutations in LMNA gene.

关 键 词：早老症 LMNA基因 家系研究 

分 类 号：R725.9[医药卫生—儿科]