Abstract
Molecular analysis of an unusual patient with the Lesch-Nyhan syndrome has suggested that the mutation is due to a partial HPRTgene duplication. We now report the cloning and sequencing of the mutant HPRTcDNA which shows the precise duplication of exons 2 and 3. This mutation is the result of an internal duplication of 16–20 kilobases of the gene. The structure of the mutant gene suggests that the duplication was not generated by a single unequal crossing-over event between two normal HPRTalleles. Growth of Epstein-Barr virus-transformed lymphoblasts from this patient in selective medium has permitted isolation of spontaneous HPRT+ revertants of this mutation. The reversion event involves a second major HPRTgene rearrangement where most or all of the duplicated portion of the mutant gene is deleted. The original mutation therefore has the potential for spontaneous somatic reversion. This may explain the relatively mild symptoms of the Lesch-Nyhan syndrome exhibited by this patient.
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Yang, T.P., Stout, J.T., Konecki, D.S. et al. Spontaneous reversion of novel Lesch-Nyhan mutation byHPRT gene rearrangement. Somat Cell Mol Genet 14, 293–303 (1988). https://doi.org/10.1007/BF01534590
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DOI: https://doi.org/10.1007/BF01534590