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Published online before print March 18, 2009, doi:10.1212/01.wnl.0000346518.68110.60)
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Received November 25, 2008
Accepted January 14, 2009

Congenital muscular dystrophies with defective glycosylation of dystroglycan. A population study

E. Mercuri MD, PhD*, S. Messina MD, PhD, C. Bruno MD, PhD, M. Mora PhD, E. Pegoraro MD, PhD, G. P. Comi MD, PhD, A. D'Amico MD, C. Aiello PhD, R. Biancheri MD, A. Berardinelli MD, PhD, P. Boffi MD, D. Cassandrini PhD, A. Laverda PhD, M. Moggio MD, PhD, L. Morandi MD, PhD, I. Moroni MD, M. Pane MD, R. Pezzani PhD, A. Pichiecchio MD, PhD, A. Pini MD, PhD, C. Minetti MD, PhD, T. Mongini MD, PhD, E. Mottarelli PhD, E. Ricci MD, PhD, A. Ruggieri PhD, S. Saredi PhD, C. Scuderi MD, A. Tessa PhD, A. Toscano MD, PhD, G. Tortorella MD, PhD, C. P. Trevisan MD, PhD, C. Uggetti MD, PhD, G. Vasco MD, F. M. Santorelli PhD, and E. Bertini MD, PhD

From the Department of Paediatric Neurology (E.M., S.M., M.P., A. Pini, G.V.) and Institute of Neurology (E.R.), Catholic University, Rome; Department of Neurosciences, Psychiatry and Anaesthesiology (S.M., A. Toscano) and Unit of Child Neuropsychiatry, Department of Pediatrics (G.T.), University of Messina; Muscular and Neurodegenerative Disease and Child Neurology and Psychiatry Units (C.B., R.B., D.C., C.M.), G. Gaslini Institute, Genoa; Myopathology and Neuroimmunology and Pediatric Neurology Units (M. Mora, L.M., I.M., E.M., A.R., S.S.), Neurological Institute C. Besta, Milan; Departments of Neurosciences and Paediatrics (E.P., A.L., R.P., C.P.T.), University of Padua; Dino Ferrari Centre (G.P.C., M. Moggio), Department of Neurological Sciences, University of Milan, Foundation I.R.C.C.S. Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan; Department of Laboratory Medicine (A.D., C.A., A. Tessa, F.M.S., E.B.), Bambino Gesù Hospital, Rome; IRCCS "C. Mondino" Foundation (A.B., A. Pichiecchio, C.U.), University of Pavia; Department of Child Neuropsychiatry (P.B.) and Neuromuscular Center, S.G. Battista Hospital (T.M.), University of Turin; Child Neurology and Psychiatry Unit, Maggiore Hospital, University of Bologna, Italy; and Neurological Unit (C.S.), IRCCS Oasi Maria SS, Troina, Italy.


* To whom correspondence should be addressed. E-mail: mercuri{at}rm.unicatt.it.

Background: 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.

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 {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).

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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Abnormal glycosylation of the {alpha}-dystroglycan: Deficient sugars are no good
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Neurology 2009 72: 1798-1799. [Full Text] [PDF]



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H. Topaloglu
Abnormal glycosylation of the {alpha}-dystroglycan: Deficient sugars are no good
Neurology, May 26, 2009; 72(21): 1798 - 1799.
[Full Text] [PDF]


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