Laminin α2 muscular dystrophy: Genotype/phenotype studies of 22 patients

Elena Pegoraro, H. Marks, C. A. Garcia, T. Crawford, P. Mancias, A. M. Connolly, M. Fanin, F. Martinello, C. P. Trevisan, C. Angelini, A. Stella, M. Scavina, R. L. Munk, S. Servidei, C. C. Bönnemann, T. Bertorini, G. Acsadi, C. E. Thompson, D. Gagnon, G. HogansonV. Carver, R. A. Zimmerman, E. P. Hoffman

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Objective: To determine the number of primary laminin α2 gene mutations and to conduct genotype/phenotype correlation in a cohort of laminin α2- deficient congenital muscular dystrophy patients. Background: Congenital muscular dystrophies (CMD) are a heterogeneous group of muscle disorders characterized by early onset muscular dystrophy and a variable involvement of the CNS. Laminin α2 deficiency has been reported in about 40 to 50% of cases of the occidental, classic type of CMD. Laminin α2 is a muscle specific isoform of laminin localized to the basal lamina of muscle fibers, where it is thought to interact with myofiber membrane receptor, such as integrins, and possibly dystrophin-associated glycoproteins. Methods: Seventy-five CMD patients were tested for laminin α2 expression by immunofluorescence and immunoblot. The entire 10 kb laminin α2 coding sequence of 22 completely laminin α2-deficient patients was screened for causative mutations by reverse transcription (RT)-PCR/single strand conformational polymorphisms (SSCP) analysis and protein truncation test (PTT) analysis followed by automatic sequencing of patient cDNA. Clinical data from the laminin α2- deficient patients were collected. Results: Thirty laminin α2-negative patients were identified (40% of CMD patients tested) and 22 of them were screened for laminin α2 mutations. Clinical features of laminin α2- deficient patients were similar, with severe floppiness at birth, delay in achievement of motor milestones, and MRI findings of white matter changes with normal intelligence. Loss-of-function mutations were identified in 95% (21/22) of the patients studied. SSCP analysis detected laminin α2 gene mutations in about 50% of the mutant chromosomes; PTT successfully identified 75% of the mutations. A two base pair deletion mutation at position 2,096- 2,097 bp was present in 23% of the patients analyzed. Conclusions: Our data suggest that the large majority of laminin α2-deficient patients show laminin α2 gene mutations.

Original languageEnglish (US)
Pages (from-to)101-110
Number of pages10
JournalNeurology
Volume51
Issue number1
DOIs
StatePublished - Jul 1998

ASJC Scopus subject areas

  • Clinical Neurology

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    Pegoraro, E., Marks, H., Garcia, C. A., Crawford, T., Mancias, P., Connolly, A. M., Fanin, M., Martinello, F., Trevisan, C. P., Angelini, C., Stella, A., Scavina, M., Munk, R. L., Servidei, S., Bönnemann, C. C., Bertorini, T., Acsadi, G., Thompson, C. E., Gagnon, D., ... Hoffman, E. P. (1998). Laminin α2 muscular dystrophy: Genotype/phenotype studies of 22 patients. Neurology, 51(1), 101-110. https://doi.org/10.1212/WNL.51.1.101