Phosphofructokinase deficiency: recent advances in molecular biology.

Phosphofructokinase (PFK) plays a major role in glycolysis. Deficiency of PFK-M is characterized by muscle weakness due to fuel crisis in exercising muscles. To elucidate the gene defect of PFK-deficient patients, we have cloned and determined the complete structure and transcription mechanism of human PFK-M mRNA and gene. Molecular defects were investigated in three unrelated Japanese family cases. The first case was characterized by a point mutation at the donor site of intron 15 of the PFK-M gene. Cryptic splicing resulted in a 25 amino acid truncation in the patient's PFK-M. The second case possessed a point mutation at the donor site of intron 19, resulting in the skipping of exon 19 and the truncation of 55 amino acids. In the third case, a missense mutation was identified in the coding region. The review of an updated mutation repertoire indicates the heterogeneity of the molecular mechanism of the disease.