Blood, Vol. 96 No. 3 (August 1), 2000:
pp. 1130-1135
Triose phosphate isomerase deficiency in 3 French families: two
novel null alleles, a frameshift mutation (TPI Alfortville) and an
alteration in the initiation codon (TPI Paris)
Colette Valentin,
Serge Pissard,
Josiane Martin,
Delphine Héron,
Philippe Labrune,
Marie-Odile Livet,
Michèle Mayer,
Terri Gelbart,
Arthur Schneider,
Isabelle Max-Audit, and
Michel Cohen-Solal
From Unité INSERM U474 and Laboratoire de
Biochimie-Génétique, Hôpital Henri Mondor,
Créteil, France; Service de Pédiatrie et de
Génétique, Groupe Hospitalier
Pitié-Salpétrière, Paris, France; Service de
Pédiatrie and UPRES UA2704, Hôpital Antoine
Béclère, Clamart, France; Service de Pédiatrie,
Centre Hospitalier de Pays d'Aix, Aix en Provence, France; Service de
Neuropédiatrie, Hôpital Saint Vincent de Paul, Paris,
France; Department of Molecular and Experimental Medicine, The Scripps
Research Institute, La Jolla, CA; Department of Pathology, Finch
University of Health Sciences/The Chicago Medical School, North
Chicago, IL.
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 with the frequent
E105D mutation. The second mutation occurred in association with the
2-nucleotide promoter variant (
43G,46A). In a third family, the
propositus was an E105D homozygote. In the TPI Paris family, the
coinheritance of the 43,46 promoter variant appeared to exert
little, if any, effect on TPI enzyme activity, a finding consistent
with 2 previous reports that questioned the putative role of the
promoter polymorphism as a true deficiency variant. Similarly, the
further coinheritance of glucose-6-phosphate dehydrogenase (G6PD)
A (202 GA/376 AG) appeared to have
little effect on the observed phenotype. Compound heterozygosity for the E105D mutation with the null allele TPI Alfortville appeared to
lead to a more severe clinical syndrome than did E105D homozygosity, suggesting that compound heterozygosity with null alleles may lead to
more profound clinical abnormalities than homozygosity with missense
alleles. A simple, rapid polymerase chain reaction and restriction
enzyme procedure for the E105D mutation was developed for prenatal
diagnosis in one family and subsequently used for screening in the
other families.
