Novel compound heterozygous laminina2-chain gene (LAMA2) mutations in congenital muscular dystrophy. Mutations in brief no. 159. Online.

J. T. Mendell, S. G. Panicker, C. Y. Tsao, B. Feng, Z. Sahenk, G. A. Marzluf, J. R. Mendell

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The laminina2-chain gene (LAMA2) encodes a basal lamina protein, laminina2, known to be deficient in one form of congenital muscular dystrophy (CMD). In a laminina2 deficient-CMD patient, we screened the entire LAMA2 cDNA (953bp) by reverse transcriptase polymerase chain reaction combined with single strand conformational polymorphism analysis. Direct sequencing of aberrant conformers in this patient revealed two loss-of-function mutations, consistent with autosomal recessive inheritance. The patient had two novel heterozygous mutations: 1) an exon 4 nonsense mutation caused by a G-->A substitution at cDNA position 547, changing the TGG codon for tryptophan into a TGA stop codon (W166X) in the N-terminus domain VI;ii) an exon 54 frameshift mutation due to a deletion of nucleotide 'C' at cDNA position 7707 (S2553Y), resulting in a premature stop codon (V2587X) in exon 55 in the globular G domain of laminina2 at the C-terminus. These mutations cause a disruption of the open reading frame of LAMA2. The absence of laminina2 observed in the patient's muscle biopsy could result from diminished levels of the LAMA2 transcript. Alternatively, the mutations might lead to translation of a truncated laminina2. By either mechanism the phenotype of congenital muscular dystrophy is believed to be the result of disruption of linkage between the extracellular matrix and the dystrophin glycoprotein complex.

Original languageEnglish (US)
Pages (from-to)135
Number of pages1
JournalHuman Mutation
Volume12
Issue number2
StatePublished - 1998

Fingerprint

Muscular Dystrophies
Exons
Mutation
Complementary DNA
Terminator Codon
Nonsense Codon
Genes
Dystrophin
Frameshift Mutation
Reverse Transcriptase Polymerase Chain Reaction
Basement Membrane
Codon
Tryptophan
Open Reading Frames
Extracellular Matrix
Glycoproteins
Nucleotides
Phenotype
Biopsy
Muscles

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Mendell, J. T., Panicker, S. G., Tsao, C. Y., Feng, B., Sahenk, Z., Marzluf, G. A., & Mendell, J. R. (1998). Novel compound heterozygous laminina2-chain gene (LAMA2) mutations in congenital muscular dystrophy. Mutations in brief no. 159. Online. Human Mutation, 12(2), 135.

Novel compound heterozygous laminina2-chain gene (LAMA2) mutations in congenital muscular dystrophy. Mutations in brief no. 159. Online. / Mendell, J. T.; Panicker, S. G.; Tsao, C. Y.; Feng, B.; Sahenk, Z.; Marzluf, G. A.; Mendell, J. R.

In: Human Mutation, Vol. 12, No. 2, 1998, p. 135.

Research output: Contribution to journalArticle

Mendell, JT, Panicker, SG, Tsao, CY, Feng, B, Sahenk, Z, Marzluf, GA & Mendell, JR 1998, 'Novel compound heterozygous laminina2-chain gene (LAMA2) mutations in congenital muscular dystrophy. Mutations in brief no. 159. Online.', Human Mutation, vol. 12, no. 2, pp. 135.
Mendell, J. T. ; Panicker, S. G. ; Tsao, C. Y. ; Feng, B. ; Sahenk, Z. ; Marzluf, G. A. ; Mendell, J. R. / Novel compound heterozygous laminina2-chain gene (LAMA2) mutations in congenital muscular dystrophy. Mutations in brief no. 159. Online. In: Human Mutation. 1998 ; Vol. 12, No. 2. pp. 135.
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