title: Identification of three novel mutations in non-Ashkenazi Italian patients with muscle phosphofructokinase deficiency.
abstract: We have identified three novel mutations in four non-Ashkenazi Italian patients with muscle phosphofructokinase (PFK-M) deficiency (Tarui disease). 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-junction 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 homozygous for a G-to-C substitution at codon 39, changing an encoded arginine (CGA) to proline (CCA). Patient 3 was heterozygous for an A-to-C substitution at codon 543, changing an encoded aspartate (GAC) to alanine (GCC); the PFK-M gene on the other allele was not expressed, but sequencing of the reported regulatory region of the gene did not reveal any mutation.
authors.affiliation: H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Disease, Department of Neurology, Columbia-Presbyterian Medical Center, New York, NY.
authors.forename: S
authors.initials: S
authors.lastname: Tsujino
authors.forename: S
authors.initials: S
authors.lastname: Servidei
authors.forename: P
authors.initials: P
authors.lastname: Tonin
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: G
authors.initials: G
authors.lastname: Azan
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon; D016384:Consensus Sequence; D017931:DNA Primers; D005091:Exons; D006014:Glycogen Storage Disease Type VII / Q000201:enzymology / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D007558:Italy; D007585:Jews; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology*; D010732:Phosphofructokinase-1 / Q000172:deficiency* / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification
chemical_list: D003062:Codon; D017931:DNA Primers; D012313:RNA; D010732:Phosphofructokinase-1