Molecular analysis of the AGL gene: heterogeneity of mutations in patients with glycogen storage disease type III from Germany, Canada, Afghanistan, Iran, and Turkey.
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.
Endo
Yoriko
Y
Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Horinishi
Asako
A
Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Vorgerd
Matthias
M
Department of Neurology, Ruhr University Bochum, Bochum, Germany.
Aoyama
Yoshiko
Y
Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Ebara
Tetsu
T
Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Murase
Toshio
T
Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Odawara
Masato
M
Third Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan.
Podskarbi
Teodor
T
Molecular Genetics and Metabolism Laboratory, Munich, Germany.
Shin
Yoon S
YS
Department of Pediatrics, University of Munich, Munich, Germany.
Okubo
Minoru
M
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.
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
D006004:Glycogen Debranching Enzyme System