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.
Valentin
C
C
Unité INSERM U474 and Laboratoire de Biochimie-Génétique, Hôpital Henri Mondor, Créteil, France.
Pissard
S
S
Martin
J
J
Héron
D
D
Labrune
P
P
Livet
M O
MO
Mayer
M
M
Gelbart
T
T
Schneider
A
A
Max-Audit
I
I
Cohen-Solal
M
M
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