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

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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
Pages (from-to)101-110
Number of pages10
JournalNeurology
Volume51
Issue number1
StatePublished - Jan 1 1998
Externally publishedYes

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Muscular Dystrophies
Laminin
Genotype
Phenotype
Mutation
Genes
Muscles
Dystrophin
Sequence Deletion
Genetic Association Studies
Muscular Diseases
Intelligence
Basement Membrane
Integrins
Base Pairing
Reverse Transcription
Fluorescent Antibody Technique
Glycoproteins
Protein Isoforms
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pegoraro, E., Marks, H., Garcia, C. A., Crawford, T., Mancias, P., Connolly, A. M., ... Hoffman, E. P. (1998). Laminin α2 muscular dystrophy: Genotype/phenotype studies of 22 patients. Neurology, 51(1), 101-110.

Laminin α2 muscular dystrophy : Genotype/phenotype studies of 22 patients. / Pegoraro, Elena; 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.; Hoganson, G.; Carver, V.; Zimmerman, R. A.; Hoffman, E. P.

In: Neurology, Vol. 51, No. 1, 01.01.1998, p. 101-110.

Research output: Contribution to journalArticle

Pegoraro, E, Marks, H, Garcia, CA, Crawford, T, Mancias, P, Connolly, AM, Fanin, M, Martinello, F, Trevisan, CP, Angelini, C, Stella, A, Scavina, M, Munk, RL, Servidei, S, Bönnemann, CC, Bertorini, T, Acsadi, G, Thompson, CE, Gagnon, D, Hoganson, G, Carver, V, Zimmerman, RA & Hoffman, EP 1998, 'Laminin α2 muscular dystrophy: Genotype/phenotype studies of 22 patients', Neurology, vol. 51, no. 1, pp. 101-110.
Pegoraro E, Marks H, Garcia CA, Crawford T, Mancias P, Connolly AM et al. Laminin α2 muscular dystrophy: Genotype/phenotype studies of 22 patients. Neurology. 1998 Jan 1;51(1):101-110.
Pegoraro, Elena ; 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. ; Hoganson, G. ; Carver, V. ; Zimmerman, R. A. ; Hoffman, E. P. / Laminin α2 muscular dystrophy : Genotype/phenotype studies of 22 patients. In: Neurology. 1998 ; Vol. 51, No. 1. pp. 101-110.
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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.",
author = "Elena Pegoraro and H. Marks and Garcia, {C. A.} and T. Crawford and P. Mancias and Connolly, {A. M.} and M. Fanin and F. Martinello and Trevisan, {C. P.} and C. Angelini and A. Stella and M. Scavina and Munk, {R. L.} and S. Servidei and B{\"o}nnemann, {C. C.} and T. Bertorini and G. Acsadi and Thompson, {C. E.} and D. Gagnon and G. Hoganson and V. Carver and Zimmerman, {R. A.} and Hoffman, {E. P.}",
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T1 - Laminin α2 muscular dystrophy

T2 - Genotype/phenotype studies of 22 patients

AU - Pegoraro, Elena

AU - Marks, H.

AU - Garcia, C. A.

AU - Crawford, T.

AU - Mancias, P.

AU - Connolly, A. M.

AU - Fanin, M.

AU - Martinello, F.

AU - Trevisan, C. P.

AU - Angelini, C.

AU - Stella, A.

AU - Scavina, M.

AU - Munk, R. L.

AU - Servidei, S.

AU - Bönnemann, C. C.

AU - Bertorini, T.

AU - Acsadi, G.

AU - Thompson, C. E.

AU - Gagnon, D.

AU - Hoganson, G.

AU - Carver, V.

AU - Zimmerman, R. A.

AU - Hoffman, E. P.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - 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.

AB - 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.

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