Evidence for founder effect of the glu104asp substitution and identification of new mutations in triosephosphate isomerase deficiency

Triosephosphate isomerase (TPI) deficiency is an autosomal recessive disorder of glycolysis characterized by multisystem disease and lethality in early childhood. Among seven unrelated Northern European kindreds with clinical TPI deficiency studied, a single missense mutation at codon 104 (GAG;Glu→GAC;Asp) predominated, accounting for 11/14 (79%) mutant alleles. In three families molecular analysis revealed compound heterozygosity for Glu104Asp and novel missense mutations. In two cases the second mutation was a Cys to Tyr substitution at codon 41(TGT→TAT) and in one an Ile to Val substitution at codon 170(ATT→GTT). The origin of the Glu104Asp mutation was defined by haplotype analysis using a novel G/A polymorphism at nucleotide 2898 of the TPI gene. Cosegregation of the low frequency 2898A allele with the G→C base change at nucleotide 315 supports a single origin for the Glu104Asp mutation in a common ancestor. Hum Mutat 10:290–294, 1997. © 1997 Wiley‐Liss, Inc.