Severe congenital muscular dystrophy in a Mexican family with a new nonsense mutation (R2578X) in the laminin α-2 gene

 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 α2 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 α2. In contrast, expression of α-, β-, γ-, and δ-sarcoglycans and dystrophin, all components of the dystrophin–glycoprotein complex, appeared normal. A homozygous C  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 α2 gene (LAMA2). Sequence analysis on available DNA samples of the family showed that parents and other relatives were carriers of the mutation. Received: August 22, 2002 / Accepted: November 11, 2002 Acknowledgments The authors wish to thank Dr. Pascale Guicheney (INSERMU523, Institute de Myologie), who kindly provided us with the primers' sequences and PCR conditions to amplify exons of LAMA2. This work was supported by CONACYT (Mexico) grant 34603-M, and Fondo de Fomento para la Investigacion-IMSS (Mexico) grant FP-0038/764. All DNA sequencing was carried out at the Centro de Instrumentos del Instituto Mexicano del Seguro Social (IMSS), Mexico City. The first two authors contributed equally to this work. Correspondence to:R.M. Coral-Vazquez