Coral-Vazquez Ramon M, Rosas-Vargas Haydee, Meza-Espinosa Pedro, Mendoza Irma, Huicochea Juan C, Ramon Guillermo, Salamanca Fabio
Unit of Medical Research in Human Genetics, Children's Hospital, XXI Century National Medical Center-IMSS, AV Cuauhtemoc No. 330, Col. Doctores, Delegacion Cuauhtemoc, Mexico City 06725, Mexico.
J Hum Genet. 2003;48(2):91-5. doi: 10.1007/s100380300013.
The congenital muscular dystrophies (CMDs) are a heterogeneous group of autosomal recessive disorders. Approximately one half of cases diagnosed with classic CMD show primary deficiency of the laminin alpha2 chain of merosin. Complete absence of this protein is usually associated with a severe phenotype characterized by drastic muscle weakness and characteristic changes in white matter in cerebral magnetic resonance imaging (MRI). Here we report an 8-month-old Mexican female infant, from a consanguineous family, with classical CMD. Serum creatine kinase was elevated, muscle biopsy showed dystrophic changes, and there were abnormalities in brain MRI. Immunofluorescence analysis demonstrated the complete absence of laminin alpha2. In contrast, expression of alpha-, beta-, gamma-, and delta-sarcoglycans and dystrophin, all components of the dystrophin-glycoprotein complex, appeared normal. A homozygous C long right arrow T substitution at position 7781 that generated a stop codon in the G domain of the protein was identified by mutation analysis of the laminin alpha2 gene ( LAMA2). Sequence analysis on available DNA samples of the family showed that parents and other relatives were carriers of the mutation.
先天性肌营养不良症（CMD）是一组常染色体隐性遗传的异质性疾病。在诊断为典型CMD的病例中，约有一半显示merosin层粘连蛋白α2链原发性缺乏。该蛋白完全缺失通常与严重表型相关，其特征为严重肌无力以及脑磁共振成像（MRI）中白质的特征性改变。在此，我们报告一名来自近亲家庭的8个月大墨西哥女婴，患有典型CMD。血清肌酸激酶升高，肌肉活检显示营养不良性改变，脑MRI有异常。免疫荧光分析显示层粘连蛋白α2完全缺失。相比之下，抗肌萎缩蛋白糖蛋白复合物的所有成分α-、β-、γ-和δ-肌聚糖以及抗肌萎缩蛋白的表达似乎正常。通过对层粘连蛋白α2基因（LAMA2）进行突变分析，在第7781位发现了一个纯合的C突变为T的替换，该替换在该蛋白的G结构域中产生了一个终止密码子。对该家庭可用DNA样本的序列分析表明，父母和其他亲属是该突变的携带者。
