title: Identical germ-line mutations in the triosephosphate isomerase alleles of two brothers are associated with distinct clinical phenotypes.
abstract: We describe here a new stop mutation at triosephosphate isomerase (TPI) position 145 in a Hungarian family for which the first mutation (240 Phe-->Leu) was published earlier. The entire genomic TPI locus (exons, introns and promoter) was sequenced and found to be identical in the two compound-heterozygote brothers. Both brothers have the same well-compensated level of non-spherocytic hemolytic anemia and very high levels of the TPI substrate dihydroxyacetonephosphate (DHAP), but only one brother manifests neurologic disorders. Differences in nonsense-mediated mRNA decay may be at the basis of the differences in phenotype expression although it cannot be excluded the interaction with a modifier gene. Based on our earlier results, the development of neurodegeneration may be decisively modulated by the cellular environment of the mutant proteins initiating the process of focal apoptosis of neurons in glycolytic, peroxisomal and prion-induced neurological diseases.
authors.affiliation: Unité Inserm U474, Maternité de Port-Royal, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Valentin
authors.forename: M
authors.initials: M
authors.lastname: Cohen-Solal
authors.forename: L
authors.initials: L
authors.lastname: Maquat
authors.forename: M
authors.initials: M
authors.lastname: Horányi
authors.forename: M
authors.initials: M
authors.lastname: Inselt-Kovács
authors.forename: S
authors.initials: S
authors.lastname: Hollán
mesh_terms: D000483:Alleles; D017931:DNA Primers; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D006814:Hungary; D007930:Leucine; D008297:Male; D009679:Nuclear Family; D010641:Phenotype; D010649:Phenylalanine; D014305:Triose-Phosphate Isomerase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*
chemical_list: D017931:DNA Primers; D010649:Phenylalanine; D014305:Triose-Phosphate Isomerase; D007930:Leucine