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PolyPhen-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PolyPhen-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 atypical progeria was assembled. Genomic DNA was extracted from peripheral blood of 5 family members, the 12 exons of LMNA gene were amplified 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 recessive inheritance pattern in this family. Conclusions The 2 siblings with MADA in this family were caused by compound heterozygous mutations in LMNA gene.