title: McArdle disease: the mutation spectrum of PYGM in a large Italian cohort.
abstract: Deficiency of the muscle isozyme of glycogen phosphorylase is causative of McArdle disease or Glycogen storage disease type V (GSD-V), the most common autosomal recessive disorder of glycogen metabolism. The typical clinical presentation is characterized by exercise intolerance with cramps, and recurrent myoglobinuria. To date, 46 mutations in the PYGM gene have been detected in GSD-V patients. We report the mutational spectrum in 68 Italian patients. We identified 30 different mutations in the PYGM gene, including 19 mutations that have not been reported previously. The novel mutations include: eight missense mutations (c.475G>A, p.G159R; c.689C>G, p.P230R; c.1094C>T, p.A365E; c.1151C>A, p.A384D; c.1182C>T, p.R428C; c.1471C>T, p.R491C; c.2444A>C, p.D815A; c.2477G>C, p.W826S), two nonsense mutations (c.1475G>A, p.W492X; c.1627A>T, p.K543X), five splice site mutations (c.855 +1G>C; c.1092 +1G>A; c. 1093-1G>T; c.1239 +1G>A; c.2380 +1G>A), and four deletions (c.715_717delGTC, p.V239del; c.304delA, p.N102DfsX4; c.1970_2177del, p.V657_G726; c.2113_2114delGG, p.G705RfsX16). Whereas we confirmed lack of direct correlation between the clinical phenotype and the genotype, we also found that the so-called 'common mutation' (p.R50X) accounted for about 43% of alleles in our cohort and that no population-related mutations are clearly identified in Italian patients.
authors.affiliation: Neuromuscular Disease Unit, Department of Pediatrics, University of Genova, Giannina Gaslini Institute, Genova, Italy. claudiobruno@ospedale-gaslini.ge.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Denise
authors.initials: D
authors.lastname: Cassandrini
authors.forename: Andrea
authors.initials: A
authors.lastname: Martinuzzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Toscano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.forename: Serena
authors.initials: S
authors.lastname: Servidei
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mongini
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.forename: Olimpia
authors.initials: O
authors.lastname: Musumeci
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Costanza
authors.initials: C
authors.lastname: Lamperti
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Filosto
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D024982:Glycogen Phosphorylase, Muscle Form / Q000235:genetics*; D006012:Glycogen Storage Disease Type V / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D024982:Glycogen Phosphorylase, Muscle Form