TY - JOUR
T1 - Congenital muscular dystrophies with defective glycosylation of dystroglycan
T2 - A population study
AU - Mercuri, E.
AU - Messina, S.
AU - Bruno, C.
AU - Mora, M.
AU - Pegoraro, E.
AU - Comi, G. P.
AU - D'Amico, A.
AU - Aiello, C.
AU - Biancheri, R.
AU - Berardinelli, A.
AU - Boffi, P.
AU - Cassandrini, D.
AU - Laverda, A.
AU - Moggio, M.
AU - Morandi, L.
AU - Moroni, I.
AU - Pane, M.
AU - Pezzani, R.
AU - Pichiecchio, A.
AU - Pini, A.
AU - Minetti, C.
AU - Mongini, T.
AU - Mottarelli, E.
AU - Ricci, E.
AU - Ruggieri, A.
AU - Saredi, S.
AU - Scuderi, C.
AU - Tessa, A.
AU - Toscano, A.
AU - Tortorella, G.
AU - Trevisan, C. P.
AU - Uggetti, C.
AU - Vasco, G.
AU - Santorelli, F. M.
AU - Bertini, E.
PY - 2009/5/26
Y1 - 2009/5/26
N2 - BACKGROUND:: Congenital muscular dystrophies (CMD) with reduced glycosylation of alpha-dystroglycan (α-DG) are a heterogeneous group of conditions associated with mutations in six genes encoding proven or putative glycosyltransferases. OBJECTIVES:: The aim of the study was to establish the prevalence of mutations in the six genes in the Italian population and the spectrum of clinical and brain MRI findings. METHODS:: As part of a multicentric study involving all the tertiary neuromuscular centers in Italy, FKRP, POMT1, POMT2, POMGnT1, fukutin, and LARGE were screened in 81 patients with CMD and α-DG reduction on muscle biopsy (n = 76) or with a phenotype suggestive of α-dystroglycanopathy but in whom a muscle biopsy was not available for α-DG immunostaining (n = 5). RESULTS:: Homozygous and compound heterozygous mutations were detected in a total of 43/81 patients (53%), and included seven novel variants. Mutations in POMT1 were the most prevalent in our cohort (21%), followed by POMT2 (11%), POMGnT1 (10%), and FKRP (9%). One patient carried two heterozygous mutations in fukutin and one case harbored a new homozygous variant in LARGE. No clear-cut genotype-phenotype correlation could be observed with each gene, resulting in a wide spectrum of clinical phenotypes. The more severe phenotypes, however, appeared to be consistently associated with mutations predicted to result in a severe disruption of the respective genes. CONCLUSIONS:: Our data broaden the clinical spectrum associated with mutations in glycosyltransferases and provide data on their prevalence in the Italian population.
AB - BACKGROUND:: Congenital muscular dystrophies (CMD) with reduced glycosylation of alpha-dystroglycan (α-DG) are a heterogeneous group of conditions associated with mutations in six genes encoding proven or putative glycosyltransferases. OBJECTIVES:: The aim of the study was to establish the prevalence of mutations in the six genes in the Italian population and the spectrum of clinical and brain MRI findings. METHODS:: As part of a multicentric study involving all the tertiary neuromuscular centers in Italy, FKRP, POMT1, POMT2, POMGnT1, fukutin, and LARGE were screened in 81 patients with CMD and α-DG reduction on muscle biopsy (n = 76) or with a phenotype suggestive of α-dystroglycanopathy but in whom a muscle biopsy was not available for α-DG immunostaining (n = 5). RESULTS:: Homozygous and compound heterozygous mutations were detected in a total of 43/81 patients (53%), and included seven novel variants. Mutations in POMT1 were the most prevalent in our cohort (21%), followed by POMT2 (11%), POMGnT1 (10%), and FKRP (9%). One patient carried two heterozygous mutations in fukutin and one case harbored a new homozygous variant in LARGE. No clear-cut genotype-phenotype correlation could be observed with each gene, resulting in a wide spectrum of clinical phenotypes. The more severe phenotypes, however, appeared to be consistently associated with mutations predicted to result in a severe disruption of the respective genes. CONCLUSIONS:: Our data broaden the clinical spectrum associated with mutations in glycosyltransferases and provide data on their prevalence in the Italian population.
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U2 - 10.1212/01.wnl.0000346518.68110.60
DO - 10.1212/01.wnl.0000346518.68110.60
M3 - Article
C2 - 19299310
AN - SCOPUS:67649229495
VL - 72
SP - 1802
EP - 1809
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 21
ER -