Abstract.
Intracellular concentrations of the nucleotide inosine triphosphate (ITP) are regulated by ITP-ase (EC 3.6.1.19), which is encoded by ITPA on chromosome 20p. Subjects with complete deficiency of ITP-ase activity (MIM 147520) have elevated ITP concentrations in erythrocytes, but no obvious clinical abnormalities. Based on biochemical screening, complete ITP-ase deficiency has been postulated to result from homozygosity for a dysfunctional allele, with an estimated frequency of 0.05 in Caucasians. ITP-ase deficiency has not yet been characterized at the molecular genetic level. Sequencing of the genomic DNA from a Caucasian subject with complete ITP-ase deficiency revealed homozygosity for missense mutation 198C>A, which predicted a threonine for proline substitution at codon 32 (P32T), whereas among 125 normal Caucasians, there were no homozygotes for P32T (P = 0.0079). The P32T allele frequency of 0.07 in Caucasians was similar to the estimates derived from earlier biochemical studies. P32T was found to be present at varying frequency in other ethnic groups. Two common synonymous single-nucleotide polymorphisms were also identified. These ITPA markers, including P32T, provide tools for further study of association with clinical and biochemical phenotypes.
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Received: July 18, 2002 / Accepted: August 6, 2002
Acknowledgments Pearl Campbell, Cheryl Leung, and Andrea Mok provided outstanding technical assistance. Dr. Hegele holds a Canada Research Chair (Tier I) in Human Genetics and a Career Investigator Award from the Heart and Stroke Foundation of Ontario. This work was supported by grants from Canadian Institutes for Health Research (MT13430), the Canadian Genetic Diseases Network, and the Blackburn Group.
Correspondence to:R.A. Hegele
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Cao, H., Hegele, R. DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency. J Hum Genet 47, 620–622 (2002). https://doi.org/10.1007/s100380200095
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DOI: https://doi.org/10.1007/s100380200095
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