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.
Congenital muscular dystrophies with defective glycosylation of dystroglycan : a population study / E. Mercuri, S. Messina, C. Bruno, M. Mora, E. Pegoraro, G.P. Comi, A. D'Amico, C. Aiello, R. Biancheri, A. Berardinelli, P. Boffi, D. Cassandrini, A. Laverda, M. Moggio, L. Morandi, I. Moroni, M. Pane, R. Pezzani, A. Pichiecchio, A. Pini, C. Minetti, T. Mongini, E. Mottarelli, E. Ricci, A. Ruggieri, S. Saredi, C. Scuderi, A. Tessa, A. Toscano, G. Tortorella, C.P. Trevisan, C. Uggetti, G. Vasco, F.M. Santorelli, E. Bertini. - In: NEUROLOGY. - ISSN 0028-3878. - 72:21(2009 May), pp. 1802-1809.
|Titolo:||Congenital muscular dystrophies with defective glycosylation of dystroglycan : a population study|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Data di pubblicazione:||mag-2009|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1212/01.wnl.0000346518.68110.60|
|Appare nelle tipologie:||01 - Articolo su periodico|