title: DNA-based subtyping of glycogen storage disease type III: mutation and haplotype analysis of the AGL gene in Chinese.
abstract: Glycogen storage disease type III (GSD III) is an inborn error of glycogen metabolism caused by a deficiency of glycogen debranching enzyme (AGL). Here, we investigate two unrelated Hong Kong Chinese GSD III patients and identify a novel 5-base pair deletional mutation, 2715_2719delTCAGAin exon 22, in one patient and a nonsense mutation, 1222C>T (R408X) in exon 11, in another patient. Since GSD IIIb is only caused by mutation in exon 3 of the AGL gene, we diagnose our patients to have GSD IIIa, which is consistent with the clinical diagnosis. Until now, R408X has only been reported in Faroe Islands GSDIII patients and was thought to demonstrate a founder effect. In this study, haplotyping of the disease-bearing chromosomes in the AGL locus by 19 intragenic single nucleotide polymorphisms shows that R408X is linked with IVS16+8T and IVS23-21T in our patient while R408X is linked with IVS16+8C and IVS23-21A in the Faroe Islands. The different haplotypes of R408X in Chinese and Faroese indicated that R408X is a recurrent mutation.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. ching-wanlam@cuhk.edu.hk
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.forename: Allen Ting-Chun
authors.initials: AT
authors.lastname: Lee
authors.forename: Yuen-Yu
authors.initials: YY
authors.lastname: Lam
authors.forename: Tak-Wai
authors.initials: TW
authors.lastname: Wong
authors.forename: Tony Wing-Lai
authors.initials: TW
authors.lastname: Mak
authors.forename: Wai-Ching
authors.initials: WC
authors.lastname: Fung
authors.forename: Kwok-Chiu
authors.initials: KC
authors.lastname: Chan
authors.forename: Che-Shun
authors.initials: CS
authors.lastname: Ho
authors.forename: Sui-Fan
authors.initials: SF
authors.lastname: Tong
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D005453:Fluorescence; D017353:Gene Deletion; D006004:Glycogen Debranching Enzyme System / Q000235:genetics*; D006010:Glycogen Storage Disease Type III / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006723:Hong Kong; D006801:Humans; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; D017931:DNA Primers; D006004:Glycogen Debranching Enzyme System