层黏连蛋白α2缺陷型先天性肌营养不良的临床与基因分析

Clinical and genetics analysis of patients with laminin-α2 chain-deficient congenital muscular dystrophy

目的探讨层黏连蛋白α2缺陷型先天性肌营养不良的临床表现和遗传学特点。方法回顾分析3例层黏连蛋白α2缺陷型先天性肌营养不良患儿的临床表现、实验室检查、肌肉病理及基因检测资料,并复习相关文献。结果本组患儿男1例,女例2例,临床表现为出生后肌力低下,运动发育落后,1例能独走,2例能独坐。肌酸激酶(CK)中度升高(895~1414 U/L),肌酸激酶同工酶(CM-MB)轻度升高(34~94 U/L)。头颅MRI示大脑脑白质异常信号。2例患儿肌肉活检,1例Merosin部分表达减弱,局灶缺失,1例Merosin表达明显减弱或缺失。基因检测显示均检测出LAMA2基因复合杂合突变,分别是外显子无义突变(c.7147 C>T、c.7810C>T)、微缺失突变(c.6513_6515del)和内含子杂合突变(c.2451-6A>G、c.3556-13T>A)。结论层黏连蛋白α2缺陷型先天性肌营养不良表现为出生后肌力低下、运动发育落后和典型脑白质病变,肌肉活检及LAMA2基因检测可明确诊断,进行准确的遗传咨询。

Objective To investigate the clinical features and genetic characteristics of laminin-α2 chain-deficient congenital muscular dystrophy(LAMA2-MD).Methods The data of clinical manifestations,laboratory examination,muscle pathology and gene detection with LAMA2-MD in 3 children were retrospectively analyzed.Results 3 patients presented with muscle weakness and delayed motor development after birth.1 patient developed the ability to walk and 2 patients developed the ability to sit alone.Creatine kinase(CK)and CK-MB levels were elevated.Brain MRI showed white matter abnormality.Immunohistochemistry of muscle biopsy in 2 patients showed that partial absence of Merosin staining in 1patient and complete absence of Merosin staining in another patient.All of them carried compound heterozygous mutations in LAMA2 gene.Their mutations of LAMA2 gene were exon nonsense mutation(c.7147 C>T,c.7810C>T),microdeletion mutation(c.6513_6515del)and intron heterozygous mutation(c.2451-6A>G,c.3556-13T>A).Conclusion LAMA2-MD is a CMD characterized by severe muscle weakness,delayed motor development after birth and typical white matter changes.Muscle biopsy and LAMA2 gene detection can make a definite diagnosis that was useful for accurate genetic counseling.