Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Jul;90(1):130–135. doi: 10.1172/JCI115825

Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients.

N Kamatani 1, M Hakoda 1, S Otsuka 1, H Yoshikawa 1, S Kashiwazaki 1
PMCID: PMC443071  PMID: 1353080

Abstract

We analyzed mutant alleles of adenine phosphoribosyltransferase (APRT) deficiency in Japanese patients. Among 141 defective APRT alleles from 72 different families, 96 (68%), 30 (21%), and 10 (7%) had an ATG to ACG missense mutation at codon 136 (APRT*J allele), TGG to TGA nonsense mutation at codon 98, and duplication of a 4-bp sequence in exon 3, respectively. The disease-causing mutations of only four (3%) of all the alleles among Japanese remain to be elucidated. Thus, a diagnosis can be made for most of the Japanese APRT-deficient patients by identifying only three disease-causing mutations. All of the different alleles with the same mutation had the same haplotype, except for APRT*J alleles, thereby suggesting that alleles with the same mutation in different families were derived from the same ancestral gene. Evidence for a crossover or gene conversion event within the APRT gene was observed in an APRT*J mutant allele. Distribution of mutant alleles encoding APRT deficiency among the Japanese was similar to that seen in cystic fibrosis genes among Caucasians and Tay-Sachs genes among the Ashkenazi Jews.

Full text

PDF
130

Images in this article

132Image
on p.132
132Image
on p.132
132Image
on p.132

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antonarakis S. E., Kazazian H. H., Jr, Orkin S. H. DNA polymorphism and molecular pathology of the human globin gene clusters. Hum Genet. 1985;69(1):1–14. doi: 10.1007/BF00295521. [DOI] [PubMed] [Google Scholar]
  2. Arpaia E., Dumbrille-Ross A., Maler T., Neote K., Tropak M., Troxel C., Stirling J. L., Pitts J. S., Bapat B., Lamhonwah A. M. Identification of an altered splice site in Ashkenazi Tay-Sachs disease. Nature. 1988 May 5;333(6168):85–86. doi: 10.1038/333085a0. [DOI] [PubMed] [Google Scholar]
  3. Arrand J. E., Murray A. M., Spurr N. Sph I restriction fragment length polymorphism on human chromosome 16 detected with an APRT gene probe. Nucleic Acids Res. 1987 Nov 25;15(22):9615–9615. doi: 10.1093/nar/15.22.9615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chehab F. F., Johnson J., Louie E., Goossens M., Kawasaki E., Erlich H. A dimorphic 4-bp repeat in the cystic fibrosis gene is in absolute linkage disequilibrium with the delta F508 mutation: implications for prenatal diagnosis and mutation origin. Am J Hum Genet. 1991 Feb;48(2):223–226. [PMC free article] [PubMed] [Google Scholar]
  5. Cox D. W., Woo S. L., Mansfield T. DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z. Nature. 1985 Jul 4;316(6023):79–81. doi: 10.1038/316079a0. [DOI] [PubMed] [Google Scholar]
  6. Curiel D., Brantly M., Curiel E., Stier L., Crystal R. G. Alpha 1-antitrypsin deficiency caused by the alpha 1-antitrypsin Nullmattawa gene. An insertion mutation rendering the alpha 1-antitrypsin gene incapable of producing alpha 1-antitrypsin. J Clin Invest. 1989 Apr;83(4):1144–1152. doi: 10.1172/JCI113994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DiLella A. G., Marvit J., Lidsky A. S., Güttler F., Woo S. L. Tight linkage between a splicing mutation and a specific DNA haplotype in phenylketonuria. 1986 Aug 28-Sep 3Nature. 322(6082):799–803. doi: 10.1038/322799a0. [DOI] [PubMed] [Google Scholar]
  8. Hakoda M., Yamanaka H., Kamatani N., Kamatani N. Diagnosis of heterozygous states for adenine phosphoribosyltransferase deficiency based on detection of in vivo somatic mutants in blood T cells: application to screening of heterozygotes. Am J Hum Genet. 1991 Mar;48(3):552–562. [PMC free article] [PubMed] [Google Scholar]
  9. Hidaka Y., Tarlé S. A., Fujimori S., Kamatani N., Kelley W. N., Palella T. D. Human adenine phosphoribosyltransferase deficiency. Demonstration of a single mutant allele common to the Japanese. J Clin Invest. 1988 Mar;81(3):945–950. doi: 10.1172/JCI113408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kamatani N., Kuroshima S., Hakoda M., Palella T. D., Hidaka Y. Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation. Hum Genet. 1990 Oct;85(6):600–604. doi: 10.1007/BF00193582. [DOI] [PubMed] [Google Scholar]
  11. Kamatani N., Sonoda T., Nishioka K. Distribution of patients with 2,8-dihydroxyadenine urolithiasis and adenine phosphoribosyltransferase deficiency in Japan. J Urol. 1988 Dec;140(6):1470–1472. doi: 10.1016/s0022-5347(17)42075-1. [DOI] [PubMed] [Google Scholar]
  12. Kamatani N., Takeuchi F., Nishida Y., Yamanaka H., Nishioka K., Tatara K., Fujimori S., Kaneko K., Akaoka I., Tofuku Y. Severe impairment in adenine metabolism with a partial deficiency of adenine phosphoribosyltransferase. Metabolism. 1985 Feb;34(2):164–168. doi: 10.1016/0026-0495(85)90127-1. [DOI] [PubMed] [Google Scholar]
  13. Kamatani N., Terai C., Kuroshima S., Nishioka K., Mikanagi K. Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase deficiencies. Hum Genet. 1987 Feb;75(2):163–168. doi: 10.1007/BF00591080. [DOI] [PubMed] [Google Scholar]
  14. Kawaguchi R., Higashimoto H., Hikiji K., Hakoda M., Kamatani N. Detection of the most common mutation of adenine phosphoribosyltransferase deficiency among Japanese by a non-radioactive method. Clin Chim Acta. 1991 Dec 16;203(2-3):183–190. doi: 10.1016/0009-8981(91)90290-s. [DOI] [PubMed] [Google Scholar]
  15. Matsubara Y., Narisawa K., Miyabayashi S., Tada K., Coates P. M. Molecular lesion in patients with medium-chain acyl-CoA dehydrogenase deficiency. Lancet. 1990 Jun 30;335(8705):1589–1589. doi: 10.1016/0140-6736(90)91413-5. [DOI] [PubMed] [Google Scholar]
  16. Mimori A., Hidaka Y., Wu V. C., Tarlé S. A., Kamatani N., Kelley W. N., Pallela T. D. A mutant allele common to the type I adenine phosphoribosyltransferase deficiency in Japanese subjects. Am J Hum Genet. 1991 Jan;48(1):103–107. [PMC free article] [PubMed] [Google Scholar]
  17. Mutations in medium chain acyl-CoA dehydrogenase deficiency. Lancet. 1990 Sep 22;336(8717):748–749. [PubMed] [Google Scholar]
  18. Orkin S. H., Kazazian H. H., Jr, Antonarakis S. E., Goff S. C., Boehm C. D., Sexton J. P., Waber P. G., Giardina P. J. Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature. 1982 Apr 15;296(5858):627–631. doi: 10.1038/296627a0. [DOI] [PubMed] [Google Scholar]
  19. Paw B. H., Tieu P. T., Kaback M. M., Lim J., Neufeld E. F. Frequency of three Hex A mutant alleles among Jewish and non-Jewish carriers identified in a Tay-Sachs screening program. Am J Hum Genet. 1990 Oct;47(4):698–705. [PMC free article] [PubMed] [Google Scholar]
  20. Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
  21. Romeo G., Devoto M., Galietta L. J. Why is the cystic fibrosis gene so frequent? Hum Genet. 1989 Dec;84(1):1–5. doi: 10.1007/BF00210660. [DOI] [PubMed] [Google Scholar]
  22. Rotter J. I., Diamond J. M. What maintains the frequencies of human genetic diseases? Nature. 1987 Sep 24;329(6137):289–290. doi: 10.1038/329289a0. [DOI] [PubMed] [Google Scholar]
  23. Sahota A., Chen J., Asaki K., Takeuchi H., Stambrook P. J., Tischfield J. A. Identification of a common nonsense mutation in Japanese patients with type I adenine phosphoribosyltransferase deficiency. Nucleic Acids Res. 1990 Oct 11;18(19):5915–5916. doi: 10.1093/nar/18.19.5915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stambrook P. J., Dush M. K., Trill J. J., Tischfield J. A. Cloning of a functional human adenine phosphoribosyltransferase (APRT) gene: identification of a restriction fragment length polymorphism and preliminary analysis of DNAs from APRT-deficient families and cell mutants. Somat Cell Mol Genet. 1984 Jul;10(4):359–367. doi: 10.1007/BF01535631. [DOI] [PubMed] [Google Scholar]
  26. Tsuji S., Choudary P. V., Martin B. M., Stubblefield B. K., Mayor J. A., Barranger J. A., Ginns E. I. A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease. N Engl J Med. 1987 Mar 5;316(10):570–575. doi: 10.1056/NEJM198703053161002. [DOI] [PubMed] [Google Scholar]
  27. Vogelstein B., Gillespie D. Preparative and analytical purification of DNA from agarose. Proc Natl Acad Sci U S A. 1979 Feb;76(2):615–619. doi: 10.1073/pnas.76.2.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wong C., Antonarakis S. E., Goff S. C., Orkin S. H., Boehm C. D., Kazazian H. H., Jr On the origin and spread of beta-thalassemia: recurrent observation of four mutations in different ethnic groups. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6529–6532. doi: 10.1073/pnas.83.17.6529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Woo S. L., Lidsky A. S., Güttler F., Chandra T., Robson K. J. Cloned human phenylalanine hydroxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature. 1983 Nov 10;306(5939):151–155. doi: 10.1038/306151a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES