Laminin alpha2 muscular dystrophy: genotype/phenotype studies of 22 patients.

Authors

E 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 Hoganson
V Carver
R A Zimmerman
E P Hoffman

Publication/Presentation Date

7-1-1998

Abstract

OBJECTIVE: To determine the number of primary laminin alpha2 gene mutations and to conduct genotype/phenotype correlation in a cohort of laminin alpha2-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 alpha2 deficiency has been reported in about 40 to 50% of cases of the occidental, classic type of CMD. Laminin alpha2 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 alpha2 expression by immunofluorescence and immunoblot. The entire 10 kb laminin alpha2 coding sequence of 22 completely laminin alpha2-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 alpha2-deficient patients were collected.

RESULTS: Thirty laminin alpha2-negative patients were identified (40% of CMD patients tested) and 22 of them were screened for laminin alpha2 mutations. Clinical features of laminin alpha2-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 alpha2 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 alpha2-deficient patients show laminin alpha2 gene mutations.

Volume

51

Issue

1

First Page

101

Last Page

110

ISSN

0028-3878

Published In/Presented At

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., Hoganson, G., … Hoffman, E. P. (1998). Laminin alpha2 muscular dystrophy: genotype/phenotype studies of 22 patients. Neurology, 51(1), 101–110. https://doi.org/10.1212/wnl.51.1.101

Disciplines

Diagnosis | Medicine and Health Sciences | Other Analytical, Diagnostic and Therapeutic Techniques and Equipment | Radiology

PubMedID

9674786

Department(s)

Department of Radiology and Diagnostic Medical Imaging

Document Type

Article