1例肢带型肌营养不良1B型的临床和遗传学特点  

Clinical and genetic features of limb-girdle muscular dystrophy type 1B:a case report

作　　者：余欣秀 钟京梓[1] 官红林 张敏[1] 蓝丹[1] YU Xin-Xiu;ZHONG Jing-ZL GUAN Hong-Lin;ZHANG Min;LAN Dan(Department of Pediatrics,First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院儿科,广西南宁530021

出　　处：《中国当代儿科杂志》2018年第12期1015-1019,共5页Chinese Journal of Contemporary Pediatrics

摘　　要：本文报道1例LMNA基因新发剪接杂合突变所致的肢带型肌营养不良1B型(LGMD1B)。患儿表现为进行性加重的行走乏力,肩胛带肌和下肢近端肌肉无萎缩,四肢肌张力正常,上肢肌力4级、下肢肌力4级,Gower征(+);CK779U/L;肌肉病理HE染色提示肌营养不良表现,免疫组化显示LaminA蛋白表达无明显减少;二代基因测序显示患儿LMNA基因存在新发的c.810+2T>C剪接位点杂合突变,其父母LMNA基因该位点正常。GERP++RS软件预测该突变位点具有高度保守性;HumanSpliceFinder和Spliceman软件预测该突变可能为致病性突变;ExPASy预测新的剪接变体氨基酸序列变短。转录组测序提示患者肌肉的mRNA存在两种序列:一种为正常序列,占92.2%;另一种为部分4号内含子保留,占7.8%,即异常剪接变体。LGMD1B是由位于常染色体1q22的LMNA基因突变所致的常染色体显性遗传性肌病,本研究的发现扩展了LMNA基因突变谱,为LGMD1B诊断提供了帮助。This article reports a case of limb-girdle muscular dystrophy type 1B(LGMD1B) caused by a novel splicing heterozygous mutation in the LMNA gene.The proband presented with progressive aggravation of weakness in walking.There was no atrophy of the scapular muscles and the lower-extremity proximal muscles,with normal muscle tension of the extremities,grade 4 muscle strength in the upper and lower extremities,and positive Gower sign.The level of creatine kinase was 779 U/L.Muscle hematoxylin-eosin staining showed muscular dystrophy,and there was no significant reduction in the expression of Lamin A protein.Second-generation sequencing revealed a novel splicing heterozygous mutation,c.810+2 T>C,in the LMNA gene,while this locus was normal in his parents.GERP++RS software predicted that the mutation site was highly conservative.Human Splice Finder and Spliceman software predicted that the mutation might be a pathogenic mutation.ExPASy software predicted that the new amino acid sequence became shorter.There were two sequences of mRNA in the patient’s muscle: one was the normal sequence,which accounted for 92.2%; the other was partial intron 4 retention,which was the abnormal splice variant accounting for 7.8%.LGMD1B is a type of autosomal dominant inherited myopathy caused by a mutation in the LMNA gene located on the autosomal 1q22.This study extends the mutation spectrum of the LMNA gene and provides help to the diagnosis of LGMD1B.

关 键 词：肢带型肌营养不良1B型 LMNA基因 剪接突变 儿童 

分 类 号：R746.2[医药卫生—神经病学与精神病学]