Ten laminin α2-deficient patients were identified by both immunofluorescence and immunoblotting (30% of congenital muscular dystrophy patients tested). Three of the laminin α2-deficient patients were carrying a diagnosis of infantile polymyositis prior to immunostaining studies. The clinical features in the 10 merosin-deficient patients were homogeneous, with severe floppiness at birth, delay in achievement of motor milestones, and magnetic resonance imaging findings of white matter changes with normal intelligence. The 10-kb laminin α2-coding sequence was screened for causative mutations by reverse transcriptase-polymerase chain reaction/single-stranded conformational polymorphism analysis in muscle biopsy specimens from 5 patients. Followed by automatic sequencing of aberrant conformers. Clear loss-of-function deletion mutations were identified in both alleles of 1 patient. Muscle histopathology in this patient showed a striking inflammatory infiltrate of T cells and B cells. Reexamination of biopsy specimens from other laminin α2-deficient patients showed minor signs of inflammation in each. Based on these findings and the histological and clinical picture suggesting failure of muscle regeneration, a pathogenesis model for this major subset of congenital muscular dystrophy is proposed. Our data show that muscle histopathology showing a neonatal inflammatory process should be considered consistent with congenital muscular dystrophy.
ASJC Scopus subject areas
- Clinical Neurology