IDENTIFICATION OF 3 NOVEL MUTATIONS IN NON-ASHKENAZI ITALIAN PATIENTSWITH MUSCLE PHOSPHOFRUCTOKINASE DEFICIENCY

We have identified three novel mutations in four non-Ashkenazi Italian patients with muscle phosphofructokinase (PFK-M) deficiency (Tarui di sease). Patient 1 was homozygous for an A-to-C substitution at the 3' end of intron 6 of the PFK-M gene, changing the consensus splice-junct ion sequence AG to CG. The mutation leads to activation of two cryptic splice sites in exon 7, resulting in one 5 bp- and one 12 bp-deleted transcript. An affected brother was also homozygous, and both parents were heterozygous, for the splice-junction mutation. Patient 2 was hom ozygous for a G-to-C substitution at codon 39, changing an encoded arg inine (CGA) to proline (CCA). Patient 3 was heterozygous for an A-to-C substitution at codon 543, changing an encoded aspartate (GAC) to ala nine (GCC); the PFK-M gene on the other allele was not expressed, but sequencing of the reported regulatory region of the gene did not revea l any mutation.