先天性全身脂肪营养不良一家系临床及基因变异分析

目的探讨先天性全身脂肪营养不良症(CGL)的临床特征及基因变异特点。方法回顾分析1对BSCL2基因变异致CGL双胎患儿的临床资料及其家系基因检测结果。结果患儿均为男性,4月龄,均表现为全身脂肪组织消失,肝脾肿大,全身少量色素沉着。实验室检查示高三酰甘油血症。提取双胎中哥哥及父母的外周血,进行全外显子组基因测序并经Sanger测序验证,结果显示患儿存在BSCL2基因c.974 dup(p.Ile 326 HisfsTer 12)纯合变异,为致病变异,确诊为CGL2。其父母均携带c.974dup杂合变异。检测其家系10人(三代)的BSCL2基因显示,双胞胎弟弟亦为BSCL2基因c.974dup纯合变异,诊断为CGL2;其祖母、外祖父、大伯、小舅以及同胞哥哥为该位点的携带者,符合常染色体隐性的遗传规律。结论发现2例同卵双胎CGL2,国内尚未见报道。

Genetic analysis of a family congenital generalized lipodystrophy

Objective To explore the clinical characteristics and gene mutation characteristics of congenital generalized lipodystrophy (CGL).Methods Clinical data and genetic results of a twin with CGL were retrospectively analyzed.Results Both of the twins were male at the age of 4 months old,presented with similar features including the disappearance of adipose tissue throughout the body,hepatosplenomegaly,and a small amount of pigmentation all over the body.Laboratory examination revealed hypertriglyceridemia.DNA extracted from peripheral blood from the elder brother of the twin and from their parents was used for whole exome gene sequencing to identify mutations verified by Sanger sequencing.The results showed that the elder brother had a homozygous mutation of c.974dup (p.ile326hisfster12) in the BSCL2 gene,which was classified as pathogenic.Both parents carry a heterozygous mutation of c.974dup.Ten members (generation Ⅰ,Ⅱ,and Ⅲ) of the family were tested for this mutation,and the younger brother of the twin was also found a homozygous mutation of c.974dup,and his grandmother and grandfather,uncle,and their sibling brother are all carriers of the mutation,which is consistent with the autosomal recessive inheritance.Conclusion Two cases of identical twins with CGL2 were reported as the first ones in China.