Molecular analysis of glycogen storage disease type Ib: identification of a prevalent mutation among Japanese patients and assignment of a putative glucose-6-phosphate translocase gene to chromosome 11.
Glycogen storage disease type Ib (GSD-Ib) is an inborn error of metabolism with autosomal recessive inheritance, caused by defects in microsomal transport of glucose-6-phosphate. Recently, Gerin et al isolated a human cDNA encoding a putative transporter homologous to bacterial transporters of hexose-6-phosphate, and identified two mutations in its gene in two patients with GSD-Ib (9). Independently, a linkage analysis mapped the GSD-Ib gene on chromosome 11q23 (10). It remains to be elucidated whether the two genes are identical or GSD-Ib is genetically heterogeneous. We first mapped the transporter gene on chromosome 11 by using a DNA panel of human/hamster hybridoma cells. The result suggested that the GSD-Ib genes identified by the two distinct approaches may be identical and GSD-Ib was allelic. We then studied four unrelated Japanese families with GSD-Ib, and found three novel mutations: a four-base deletion/two-base insertion, a point mutation within a consensus splicing donor site, and a missense mutation (W118R). The W118R mutation was found in 4 out of 8 mutant alleles, suggesting that it is prevalent among Japanese patients.
Department of Medical Genetics, Tohoku University School of Medicine, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. skure@mail.cc.tohoku.ac.jp
S
S
Kure
Y
Y
Suzuki
Y
Y
Matsubara
O
O
Sakamoto
H
H
Shintaku
G
G
Isshiki
C
C
Hoshida
I
I
Izumi
N
N
Sakura
K
K
Narisawa
D000595:Amino Acid Sequence; D017920:Antiporters; D001692:Biological Transport / Q000235:genetics; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005808:Genes, Recessive; D008040:Genetic Linkage / Q000235:genetics; D005953:Glycogen Storage Disease Type I / Q000235:genetics*; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007564:Japan; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins; D009154:Mutation / Q000235:genetics; D010770:Phosphotransferases / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics
D017920:Antiporters; D009004:Monosaccharide Transport Proteins; C503531:SLC37A4 protein, human; C111261:glucose 6-phosphate(transporter); D010770:Phosphotransferases