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).
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 G-->A/376 A-->G) 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.
Unité INSERM U474 and Laboratoire de Biochimie-Génétique, Hôpital Henri Mondor, Créteil, France.
C
C
Valentin
S
S
Pissard
J
J
Martin
D
D
Héron
P
P
Labrune
M O
MO
Livet
M
M
Mayer
T
T
Gelbart
A
A
Schneider
I
I
Max-Audit
M
M
Cohen-Solal
D000328:Adult; D000483:Alleles; D000743:Anemia, Hemolytic / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D002648:Child; D018387:Codon, Initiator / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009468:Neuromuscular Diseases / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D013577:Syndrome; D014305:Triose-Phosphate Isomerase / Q000172:deficiency / Q000235:genetics*
D018387:Codon, Initiator; D014305:Triose-Phosphate Isomerase