TY - JOUR
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 - 1998/7
Y1 - 1998/7
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.
UR - https://www.scopus.com/pages/publications/0031594947
U2 - 10.1212/WNL.51.1.101
DO - 10.1212/WNL.51.1.101
M3 - Article
C2 - 9674786
AN - SCOPUS:0031594947
SN - 0028-3878
VL - 51
SP - 101
EP - 110
JO - Neurology
JF - Neurology
IS - 1
ER -