title: Molecular analysis of the AGL gene: heterogeneity of mutations in patients with glycogen storage disease type III from Germany, Canada, Afghanistan, Iran, and Turkey.
abstract: Glycogen storage disease type III (GSD III) is an autosomal recessive disorder characterized by excessive accumulation of abnormal glycogen in the liver and/or muscles and caused by deficiency in the glycogen debranching enzyme (AGL). Previous studies have revealed that the spectrum of AGL mutations in GSD III patients depends on ethnic grouping. We investigated nine GSD III patients from Germany, Canada, Afghanistan, Iran, and Turkey and identified six novel AGL mutations: one nonsense (W255X), three deletions (1019delA, 3202-3203delTA, and 1859-1869del11-bp), and two splicing mutations (IVS7 + 5G > A and IVS21 + 5insA), together with three previously reported ones (R864X, W1327X, and IVS21 + 1G > A). All mutations are predicted to lead to premature termination, which abolishes enzyme activity. Our molecular study on GSD III patients of different ethnic ancestry showed allelic heterogeneity of AGL mutations. This is the first AGL mutation report for German, Canadian, Afghan, Iranian and Turkish populations.
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Horinishi
authors.affiliation: Department of Neurology, Ruhr University Bochum, Bochum, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Vorgerd
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Ebara
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Murase
authors.affiliation: Third Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Odawara
authors.affiliation: Molecular Genetics and Metabolism Laboratory, Munich, Germany.
authors.forename: Teodor
authors.initials: T
authors.lastname: Podskarbi
authors.affiliation: Department of Pediatrics, University of Munich, Munich, Germany.
authors.forename: Yoon S
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. QFG00550@nifty.ne.jp.|Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan. QFG00550@nifty.ne.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Okubo
mesh_terms: D000346:Afghanistan; D002170:Canada; D004252:DNA Mutational Analysis; D005838:Genotype; D005858:Germany; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000208:ethnology* / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007492:Iran; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014421:Turkey
chemical_list: D006004:Glycogen Debranching Enzyme System