Triose phosphate isomerase deficiency in 3 French families: two novel nullalleles, a frameshift mutation (TPI Alfortville) and an alteration in the initiation codon (TPI Paris)

Three French families with triose phosphate isomerase (TPI) deficiency were studied, and 2 new mutations giving rise to null alleles were observed: a frameshift mutation with deletion of the 86-87 TG dinucleotide in codon 29 (TPI Alfortville) and a T-A transversion in nucleotide 2 of the initiation codon (TPI Paris). The first mutation occurred in compound heterozygosity w ith the frequent E105D mutation. The second mutation occurred in associatio n with the 2-nucleotide promoter variant (-43G,-46A), In a third family, th e propositus was an E105D homozygote. In the TPI Paris family, the coinheri tance of the -43,-46 promoter variant appeared to exert little, if any, eff ect on TPI enzyme activity, a finding consistent with 2 previous reports th at questioned the putative role of the promoter polymorphism as a true defi ciency variant. Similarly, the further coinheritance of glucose-6-phosphate dehydrogenase (G6PD) A- (202 G-->A/376 A-->G) appeared to have little effe ct on the observed phenotype, Compound heterozygosity for the E105D mutatio n with the null allele TPI Alfortville appeared to lead to a more severe cl inical syndrome than did E105D homozygosity, suggesting that compound heter ozygosity with null alleles may lead to more profound clinical abnormalitie s than homozygosity with missense alleles, A simple, rapid polymerase chain reaction and restriction enzyme procedure for the E105D mutation was devel oped for prenatal diagnosis in one family and subsequently used for screeni ng in the other families. (C) 2000 by The American Society of HematoloEly