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The mode of genetic transmission of a gouty family with increased phosphoribosylpyrophosphate synthetase activity

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Summary

The mode of genetic transmission of gout and increased activity of phosphoribosylpyrophosphate synthetase (PRPPS) was studied in one family. Among 15 members of Family F, two male members had gout and had PRPPS activity of erythrocyte lysates three times higher than normal subjects. Five female members had activity 2.5 times higher than normal. The difference between the activities of male and female affected members was statistically significant (P<0.05). To examine the genetic trait of this abnormal PRPPS, the incorporation of 3H-adenine into erythrocytes or lymphocytes was studied using autoradiography. The number of grains which show the uptake of labeled adenine into cells revealed a normal distribution pattern in two normal persons and in two male patients, and a mixed pattern of the two cell populations in two female affected members. These results suggested mosaicism in female members and X-linked dominant transmission of this trait. Thermal inactivation of PRPPS of an affected female was intermediate between that from a normal subject and that from the affected males. This result showed the heterogeneity of the PRPPS from the hemolysate of an affected famale. The genotype of PRPPS on the X-chromosome was assumed and the lod score between PRPPS and Xg was also estimated. From these findings and electrophoretical study, it was suggested that the abnormal enzyme was a mutant enzyme transmitted in an X-linked dominant trait, and that the mutation occurred on the structural gene of the PRPPS.

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Authors and Affiliations

  1. Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, 113, Tokyo, Japan

    Fujio Takeuchi, Eiji Yano & Yoshihiko Horiuchi

  2. Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan

    Fumio Hanaoka & Masa-atsu Yamada

  3. 2nd Department of Medicine, Faculty of Medicine, University of Teikyo, Tokyo, Japan

    Ieo Akaoka

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  1. Fujio Takeuchi
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  2. Fumio Hanaoka
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  3. Eiji Yano
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  4. Masa-atsu Yamada
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  5. Yoshihiko Horiuchi
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  6. Ieo Akaoka
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Takeuchi, F., Hanaoka, F., Yano, E. et al. The mode of genetic transmission of a gouty family with increased phosphoribosylpyrophosphate synthetase activity. Hum Genet 58, 322–330 (1981). https://doi.org/10.1007/BF00294932

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  • DOI: https://doi.org/10.1007/BF00294932

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