title: Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Child Neurology, Policlinico Gemelli, Largo Gemelli, 00168 Rome, Italy. mercuri@rm.unicatt.it
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
authors.forename: S
authors.initials: S
authors.lastname: Messina
authors.forename: C
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authors.lastname: Bruno
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authors.lastname: Mora
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authors.lastname: Pegoraro
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authors.lastname: Aiello
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authors.lastname: Biancheri
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authors.lastname: Berardinelli
authors.forename: P
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authors.lastname: Boffi
authors.forename: D
authors.initials: D
authors.lastname: Cassandrini
authors.forename: A
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authors.lastname: Laverda
authors.forename: M
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authors.lastname: Moggio
authors.forename: L
authors.initials: L
authors.lastname: Morandi
authors.forename: I
authors.initials: I
authors.lastname: Moroni
authors.forename: M
authors.initials: M
authors.lastname: Pane
authors.forename: R
authors.initials: R
authors.lastname: Pezzani
authors.forename: A
authors.initials: A
authors.lastname: Pichiecchio
authors.forename: A
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authors.lastname: Pini
authors.forename: C
authors.initials: C
authors.lastname: Minetti
authors.forename: T
authors.initials: T
authors.lastname: Mongini
authors.forename: E
authors.initials: E
authors.lastname: Mottarelli
authors.forename: E
authors.initials: E
authors.lastname: Ricci
authors.forename: A
authors.initials: A
authors.lastname: Ruggieri
authors.forename: S
authors.initials: S
authors.lastname: Saredi
authors.forename: C
authors.initials: C
authors.lastname: Scuderi
authors.forename: A
authors.initials: A
authors.lastname: Tessa
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.forename: G
authors.initials: G
authors.lastname: Tortorella
authors.forename: C P
authors.initials: CP
authors.lastname: Trevisan
authors.forename: C
authors.initials: C
authors.lastname: Uggetti
authors.forename: G
authors.initials: G
authors.lastname: Vasco
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: E
authors.initials: E
authors.lastname: Bertini
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D049030:Dystroglycans / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D016695:Glycosyltransferases / Q000235:genetics*; D006801:Humans; D007223:Infant; D007558:Italy; D008279:Magnetic Resonance Imaging; D008364:Mannosyltransferases / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D010430:Pentosyltransferases; D010641:Phenotype; D015995:Prevalence; D011506:Proteins / Q000235:genetics
chemical_list: C483081:DAG1 protein, human; C113587:FKTN protein, human; D008565:Membrane Proteins; D011506:Proteins; D049030:Dystroglycans; D016695:Glycosyltransferases; C117674:LARGE1 protein, human; D008364:Mannosyltransferases; D017351:N-Acetylglucosaminyltransferases; C443106:protein O-mannose beta-1,2-N-acetylglucosaminyltransferase; C082696:protein O-mannosyltransferase; C443107:FKRP protein, human; D010430:Pentosyltransferases