%0 Journal Article
%T Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.
%A Mercuri E
%A Messina S
%A Bruno C
%A Mora M
%A Pegoraro E
%A Comi GP
%A D'Amico A
%A Aiello C
%A Biancheri R
%A Berardinelli A
%A Boffi P
%A Cassandrini D
%A Laverda A
%A Moggio M
%A Morandi L
%A Moroni I
%A Pane M
%A Pezzani R
%A Pichiecchio A
%A Pini A
%A Minetti C
%A Mongini T
%A Mottarelli E
%A Ricci E
%A Ruggieri A
%A Saredi S
%A Scuderi C
%A Tessa A
%A Toscano A
%A Tortorella G
%A Trevisan CP
%A Uggetti C
%A Vasco G
%A Santorelli FM
%A Bertini E
%J Neurology
%V 72
%N 21
%D May 2009 26
%M 19299310
%F 11.8
%R 10.1212/01.wnl.0000346518.68110.60
%X <B>BACKGROUND: </B>Congenital muscular dystrophies (CMD) with reduced glycosylation of alpha-dystroglycan (alpha-DG) are a heterogeneous group of conditions associated with mutations in six genes encoding proven or putative glycosyltransferases.<BR><B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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 alpha-DG reduction on muscle biopsy (n = 76) or with a phenotype suggestive of alpha-dystroglycanopathy but in whom a muscle biopsy was not available for alpha-DG immunostaining (n = 5).<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>Our data broaden the clinical spectrum associated with mutations in glycosyltransferases and provide data on their prevalence in the Italian population.