PHOSPHOFRUCTOKINASE DEFICIENCY - RECENT ADVANCES IN MOLECULAR-BIOLOGY

Phosphofructokinase (PFK) prays 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. (C) 1995 John Wiley and Sons, Inc.