Genetic defect in muscle phosphofructokinase deficiency. Abnormal splicing of the muscle phosphofructokinase gene due to a point mutation at the 5'-splice site

J Biol Chem. 1990 Jun 5;265(16):9392-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromosome Deletion
  • Cloning, Molecular
  • DNA / genetics
  • DNA / isolation & purification
  • Exons
  • Glycogen Storage Disease / enzymology*
  • Glycogen Storage Disease Type VII / enzymology*
  • Glycogen Storage Disease Type VII / genetics
  • Humans
  • Introns
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Nucleic Acid Hybridization
  • Phosphofructokinase-1 / deficiency
  • Phosphofructokinase-1 / genetics*
  • Polymerase Chain Reaction
  • RNA Splicing*
  • RNA, Messenger / genetics

Substances

  • RNA, Messenger
  • DNA
  • Phosphofructokinase-1

Associated data

  • GENBANK/M35042
  • GENBANK/M36003