title: Mutational and haplotype analysis of AGL in patients with glycogen storage disease type III.
abstract: Glycogen storage disease type III (GSD III) is a rare autosomal recessive inherited disorder caused by a deficiency of the glycogen-debranching enzyme (AGL). We investigated two GSD III patients and identified four different mutations. Nucleotide sequence analysis revealed patient 1 of Chinese descent to be a compound heterozygote for a novel nonsense mutation, R34X, and the splicing mutation (IVS32-12A > G) reported in a Japanese patient. Patient 2 of Japanese origin was found to be compound heterozygous for a novel nonsense mutation, Y1148X, and the splicing mutation (IVS14+1G > T) that we had described previously. To determine whether splicing mutations occurred independently, we performed intense AGL haplotype analysis using 21 intragenic polymorphic markers plus a novel polymorphism IVS32-97 A/G in the vicinity of the IVS32 splicing mutation. Patient 1 of Chinese origin and the Japanese patient homozygous for the IVS32-12A > G were found to have different haplotypes, indicating the IVS32-12A > G mutation to be a recurrent mutation. This is the first recurrent mutation established by intense haplotyping in the AGL gene.
authors.affiliation: Department of Endocrinology and Metabolism, Okinaka Memorial Institute for Medical Research and Toranomon Hospital, Tokyo, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Horinishi
authors.forename: Minoru
authors.initials: M
authors.lastname: Okubo
authors.forename: Nelson L S
authors.initials: NL
authors.lastname: Tang
authors.forename: Joannie
authors.initials: J
authors.lastname: Hui
authors.forename: Ka-Fai
authors.initials: KF
authors.lastname: To
authors.forename: Tomohito
authors.initials: T
authors.lastname: Mabuchi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Okada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mabuchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Murase
mesh_terms: D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic
chemical_list: D006004:Glycogen Debranching Enzyme System