title: Genetic defect in muscle phosphofructokinase deficiency. Abnormal splicing of the muscle phosphofructokinase gene due to a point mutation at the 5'-splice site.
abstract: The genetic defect in muscle phosphofructokinase deficiency (type VII glycogenosis, Tarui disease) was investigated. Six cDNAs for muscle phosphofructokinase, including a full-length clone, were isolated from a non-amplified library of muscle from a patient. By sequence analysis of these clones, a 75-base in-frame deletion was identified. The rest of the sequence was identical to that of the normal cDNA, except for a silent base transition at position 516 (ACT (Thr) to ACC (Thr]. The deletion was located in the 3'-terminal region of exon 13 (numbered with reference to the rabbit muscle phosphofructokinase gene (Lee, C.-P., Kao, M.-C., French, B.A., Putney, S.D., and Chang, S.H. (1987) J. Biol. Chem. 262, 4195-4199]. Genomic DNA of the patient was amplified by polymerase chain reaction. Sequence analysis of the amplified DNA revealed a point mutation from G to T at the 5'-end of intron 13. This mutation changed the normal 5'-splice site of CAG:GTATGG to CAG:TTATGG. A cryptic splice site of ACT:GTGAGG located 75 bases upstream from the normal splice site was recognized and spliced in the patient.
authors: Second Department of Internal Medicine, Osaka University Medical School, Japan.
authors: H
authors: H
authors: Nakajima
authors: N
authors: N
authors: Kono
authors: T
authors: T
authors: Yamasaki
authors: K
authors: K
authors: Hotta
authors: M
authors: M
authors: Kawachi
authors: M
authors: M
authors: Kuwajima
authors: T
authors: T
authors: Noguchi
authors: T
authors: T
authors: Tanaka
authors: S
authors: S
authors: Tarui
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D006008:Glycogen Storage Disease / Q000201:enzymology*; D006014:Glycogen Storage Disease Type VII / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010732:Phosphofructokinase-1 / Q000172:deficiency / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D004247:DNA; D010732:Phosphofructokinase-1