Mutational and haplotype analysis of AGL in patients with glycogen storage disease type III.
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.
Horinishi
Asako
A
Department of Endocrinology and Metabolism, Okinaka Memorial Institute for Medical Research and Toranomon Hospital, Tokyo, Japan.
Okubo
Minoru
M
Tang
Nelson L S
NL
Hui
Joannie
J
To
Ka-Fai
KF
Mabuchi
Tomohito
T
Okada
Toshihide
T
Mabuchi
Hiroshi
H
Murase
Toshio
T
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
D006004:Glycogen Debranching Enzyme System