A NEW VARIANT OF MUSCLE PHOSPHOFRUCTOKINASE DEFICIENCY IN A JAPANESE CASE WITH ABNORMAL RNA SPLICING

A genetic defect was investigated in a newly diagnosed Japanese case w ith muscle type phosphofructokinase (PFK-M) deficiency. Polymerase cha in reaction (PCR) amplification of patient cDNA revealed an in-frame t runcation of 165 bases. This was compatible to the complete deletion o f exon 19. The rest of the sequence was identical to that of the norma l PFK-M cDNA. Sequencing of PCR amplified genomic DNA of the patient r evealed a point mutation from G to A at the 5'donor site of intron 19. This mutation resulted in the skipping of exon 19 in the patient mRNA . Homozygosity of this patient was confined by allele specific amplifi cation of the genomic DNA. Donor mutations in intron 15 and intron 5 a ssociated with different splicing errors were previously reported to c ause this disease. Thus, the human PFK-M gene mutations are heterogene ous, however, the donor mutations and splicing errors would represent one of the frequent causes of this disease. (C) 1994 Academic Press, I nc.