Document Detail


A novel laminin alpha2 isoform in severe laminin alpha2 deficient congenital muscular dystrophy.
MedLine Citation:
PMID:  11071490     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Laminin alpha2 deficiency presents at birth with muscle weakness, hypotonia, and usually asymptomatic white matter signal on MRI. Few patients with laminin alpha2 deficiency have been described with seizures and structural brain abnormalities. The reason for the variation in the severity of the clinical phenotype in congenital muscular dystrophy (CMD) with laminin alpha2 deficiency is not known.
METHODS: A patient with CMD with partial laminin alpha2 presenting with brain structural abnormalities and untreatable generalized and partial complex seizure was studied. Alternative laminin alpha2 splicing was studied by single-strand conformational polymorphism/sequencing analysis.
RESULTS: A novel laminin alpha2 isoform was identified. Nonsense laminin alpha2 mutations (stop codons) were inherited from both parents; however, one of the nonsense mutations was in a region of exon 31, which is alternatively spliced. The alternatively spliced isoform excluded one of the stop codon mutations, and was thus able to produce normal laminin alpha2 corresponding to this isoform. Laminin alpha2 immunofluorescence showed that this isoform was not evenly distributed at the muscle fiber basal lamina, but preferentially localized in discrete areas. Laminin alpha5, beta1, gamma1, and nidogen showed decreased expression by immunofluorescence.
CONCLUSIONS: The severity of this patient's phenotype may be due to overexpression of the exon 31-spliced laminin alpha2 isoform. Exon 31 lies in the IIIA domain of the laminin alpha2 protein, just proximal to the triple coil-coiled region. It is possible that chain assembly is impaired by this isoform, resulting in a loss of possible rescue mechanisms.
Authors:
E Pegoraro; M Fanin; C P Trevisan; C Angelini; E P Hoffman
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neurology     Volume:  55     ISSN:  0028-3878     ISO Abbreviation:  Neurology     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-11-08     Completed Date:  2000-12-07     Revised Date:  2012-05-09    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1128-34     Citation Subset:  AIM; IM    
Affiliation:
Department of Neurological and Psychiatric Sciences, University of Padova, Italy. elenap@ux1.unipd.it
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Alternative Splicing
Exons
Female
Humans
Laminin / analysis,  genetics*
Magnetic Resonance Imaging
Muscles / chemistry,  pathology*
Muscular Dystrophies / congenital,  genetics*,  pathology*
Mutation / genetics
Phenotype
Protein Isoforms / genetics*
Grant Support
ID/Acronym/Agency:
688//Telethon; GTF01003//Telethon; N01-HD-6-2915/HD/NICHD NIH HHS; R0I 29525//PHS HHS
Chemical
Reg. No./Substance:
0/Laminin; 0/Protein Isoforms; 0/laminin alpha 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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