【摘要】 目的探讨LAMA2基因突变致先天性肌营养不良1A型（MDC1A）的临床特征及LAMA2基因突变特点。方法对3例MDC1A患儿的临床表现、辅助检查、治疗和转归等临床资料进行总结;应用二代基因测序、生物信息分析、基因验证等技术检测致病基因,并对LAMA2基因进行突变分析。结果 3例患儿均为LAMA2基因突变致病,故MDC1A可明确诊断。3例患儿均在婴儿期起病,临床表现为运动发育落后,血生化检测示肌酸激酶、肌酸激酶同工酶升高,头颅MRI显示脑白质病变,基因检测显示LAMA2基因突变。例1 LAMA2基因外显子41-47区域的杂合缺失,c.482₄85dup, p.Glu161AspinsX;例2 LAMA2基因c.6707+1G>A杂合核苷酸变异、剪切变异,c.1300C>T杂合苷酸变异为无义突变;例3 LAMA2基因c.1326T>A、c.5476C>T复合杂合核苷酸变异。例1确诊后予短暂的康复治疗,目前能生活自理;例2确诊后未予治疗,目前仅能扶站;例3自确诊后行间断康复治疗,收效甚微,目前仅能抬头,会扶坐。结论根据患儿病史、临床表现考虑为MDC1A者,行基因检测可明确诊断。LAMA2基因突变所致先天性肌营养不良,由于突变位点不同,所导致的临床症状也会有所不同。更多还原

【Abstract】 Objective To explore the clinical characteristics and gene mutation of congenital muscular dystrophy type 1 A（MDC1 A） caused by LAMA2 gene mutation and the characteristics of LAMA2 gene mutation. Methods The clinical manifestations, auxiliary examination, treatment and prognosis of 3 cases with MDC1 A were recorded. The laboratory tests including blood chemistry, emg electromyogram, genetic metabolic screening, brain MRI were performed. LAMA2 gene mutation was analyzed by second generation gene sequencing, bioinformatics analysis and genetic verification. Results All the 3 cases were caused by LAMA2 gene mutations, thus the diagnoses of MDC1 A were established. For the 3 children, the similarities included onset in infancy, motor retardation, increased creatine kinase and creatine kinase isoenzyme, leukodystrophy in brain MRI and LAMA2 gene mutation. In case 1, LAMA2 had large loss of heterozygosity from 41 to 47 in exon, c.482₄85 dup, p.Glu161 AspinsX. In case 2,the mutations was c.6707+1 G>A, heterozygous nucleotide variation and shear mutation. The nonsense mutation was c.1300 C>T, a type of heterozygous nucleotide mutation. In case 3,the complex heterozygous nucleotide mutation was c.1326 T>A and c.5476 C>T. Case 1 had months of rehabilitation therapy, and now has life self-care ability. Case 2 received no treatment and just can only stand with support. Case 3 had more than one year of rehabilitation therapy, but just can raise her head and seat with help.Conclusions MDC1 A should be highly considered in patients with above clinical symptoms, and gene detection can help clarify the diagnosis. Congenital muscular dystrophy caused by the mutation of LAMA2 gene may have different clinical symptoms due to different mutation sites.更多还原