GLYCOGENOSIS TYPE-VII (TARUI DISEASE) IN A SWEDISH FAMILY - 2 NOVEL MUTATIONS IN MUSCLE PHOSPHOFRUCTOKINASE GENE (PFK-M) RESULTING IN INTRON RETENTIONS

Phosphofructokinase (PFK) plays a major role in glycolysis. Human PFK is composed of three isoenzyme subunits (muscle [M], liver [L], and pl atelet [P]), which are encoded by different genes. Deficiency of muscl e isoenzyme (PFK-M), glycogenosis type VII (Tarui disease), is an auto somal recessive disorder characterized by an exertional myopathy and h emolytic syndrome. Several disease-causing mutations have been identif ied in the PFK-M gene in Japanese, Ashkenazi Jewish, Italian, French C anadian, and Swiss patients. We describe the genetic defect in a Swedi sh family with affected individuals in two generations. The patients a re compound heterozygotes: two different mutations result in retention of intron 13 or intron 16 sequences into mRNA. A G1127A transition de stroys the 5' donor site of intron 13, resulting in a 155-nt retention of the intronic sequence. An a-to-g base change in intron 16 creates a new acceptor splice site, resulting in a 63-nt retention of intronic sequence. Both mutations are predicted to result in premature termina tion of translation. Some of the transcripts generated from, the intro n 16 mutated allele also contain intron 10 sequence unspliced.