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. PiniC. 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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1802-1809
Number of pages8
Issue number21
Publication statusPublished - May 26 2009

ASJC Scopus subject areas

  • Clinical Neurology


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