Human Genetics

, Volume 96, Issue 6, pp 674–680 | Cite as

Selection against blood cells deficient in hypoxanthine phosphoribosyltransferase (HPRT) in Lesch-Nyhan heterozygotes occurs at the level of multipotent stem cells

  • Masayuki Hakoda
  • Yuko Hirai
  • Mitoshi Akiyama
  • Hisashi Yamanaka
  • Chihiro Terai
  • Naoyuki Kamatani
  • Sadao Kashiwazaki
Original Investigation

Abstract

Lesch-Nyhan syndrome is caused by a severe genetic deficiency of hypoxanthine phosphoribosyltransferase (HPRT) and is characterized by central nervous system disorders, gout, and in some cases, macrocytic anemia. Women heterozygous for HPRT deficiency are healthy but their somatic cells are mosaic for enzyme deficiency owing to random inactivation of the X chromosome. Frequencies of red blood cells and T cells deficient in HPRT are significantly lower than the expected 50% in heterozygotes, suggesting that HPRT-negative blood cells are selected against in heterozygotes. To determine at which stage of hematopoiesis such selection occurs, we determined the frequencies of HPRT-negative T, B and erythroid precursor cells in three heterozygotes. Since the cloning efficiencies of T and B cells and colony forming efficiency of burst-forming unit erythroid (BFU-E) for sample from Lesch-Nyhan patients were similar to those of normal cells, HPRT deficiency does not seem to render the differentiated cells less efficient for proliferation. However, the frequencies of HPRT-negative T and B cells, and BFU-E were all less than 10% in each of the three heterozygotes. Although the frequencies of HPRT-negative cells showed tenfold variations between the heterozygotes, each heterozygote had similar frequencies of HPRT-negative cells in the three cell types. These results suggest that HPRT is important at early stages of hematopoiesis, but less so after the cells have differentiated into T cells, B cells and erythroid precursor cells.

Keywords

Anemia Somatic Cell Gout Hypoxanthine System Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Masayuki Hakoda
    • 1
  • Yuko Hirai
    • 2
  • Mitoshi Akiyama
    • 2
  • Hisashi Yamanaka
    • 1
  • Chihiro Terai
    • 1
  • Naoyuki Kamatani
    • 1
  • Sadao Kashiwazaki
    • 1
  1. 1.Institute of Rheumatology, Tokyo Women's Medical CollegeTokyoJapan
  2. 2.Department of RadiobiologyRadiation Effects Research FoundationHiroshimaJapan

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