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 ex ercising muscles. To elucidate the gene defect of PFK-deficient patien ts, we have cloned and determined the complete structure and transcrip tion mechanism of human PFK-M mRNA and gene, Molecular defects were in vestigated in three unrelated Japanese family cases. The first case wa s 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 truncatio n in the patient's PFK-M. The second case possessed a point mutation a t the donor site of intron 19, resulting in the skipping of exon 19 an d the truncation of 55 amino acids. In the third case, a missense muta tion was identified in the coding region, The review of an updated mut ation repertoire indicates the heterogeneity of the molecular mechanis m of the disease. (C) 1995 John Wiley and Sons, Inc.