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McArdle disease: the mutation spectrum of PYGM in a large Italian cohort.
- Source :
-
Human mutation [Hum Mutat] 2006 Jul; Vol. 27 (7), pp. 718. - Publication Year :
- 2006
-
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&#95;717delGTC, p.V239del; c.304delA, p.N102DfsX4; c.1970&#95;2177del, p.V657&#95;G726; c.2113&#95;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.<br /> (Copyright 2006 Wiley-Liss, Inc.)
- Subjects :
- Adolescent
Adult
Aged
Alleles
Amino Acid Sequence
Child
Cohort Studies
DNA Mutational Analysis
Female
Glycogen Storage Disease Type V epidemiology
Humans
Italy epidemiology
Male
Middle Aged
Molecular Sequence Data
Sequence Alignment
Sequence Analysis, Protein
Glycogen Phosphorylase, Muscle Form genetics
Glycogen Storage Disease Type V genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 27
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 16786513
- Full Text :
- https://doi.org/10.1002/humu.9434