{Reference Type}: Journal Article
{Title}: Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.
{Author}: Mercuri E;Messina S;Bruno C;Mora M;Pegoraro E;Comi GP;D'Amico A;Aiello C;Biancheri R;Berardinelli A;Boffi P;Cassandrini D;Laverda A;Moggio M;Morandi L;Moroni I;Pane M;Pezzani R;Pichiecchio A;Pini A;Minetti C;Mongini T;Mottarelli E;Ricci E;Ruggieri A;Saredi S;Scuderi C;Tessa A;Toscano A;Tortorella G;Trevisan CP;Uggetti C;Vasco G;Santorelli FM;Bertini E;
{Journal}: Neurology
{Volume}: 72
{Issue}: 21
{Year}: May 2009 26
{Factor}: 11.8
{DOI}: 10.1212/01.wnl.0000346518.68110.60
{Abstract}: <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.