title: Severe congenital muscular dystrophy in a Mexican family with a new nonsense mutation (R2578X) in the laminin alpha-2 gene.
abstract: 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.
authors.affiliation: 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. rmcoral@correo.unam.mx
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Coral-Vazquez
authors.forename: Haydee
authors.initials: H
authors.lastname: Rosas-Vargas
authors.forename: Pedro
authors.initials: P
authors.lastname: Meza-Espinosa
authors.forename: Irma
authors.initials: I
authors.lastname: Mendoza
authors.forename: Juan C
authors.initials: JC
authors.lastname: Huicochea
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ramon
authors.forename: Fabio
authors.initials: F
authors.lastname: Salamanca
mesh_terms: D001921:Brain / Q000473:pathology; D003241:Consanguinity; D003402:Creatine Kinase / Q000097:blood; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007797:Laminin / Q000235:genetics; D008800:Mexico; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D007797:Laminin; C102645:laminin alpha 2; D003402:Creatine Kinase