Spontaneous reversion of novel Lesch-Nyhan mutation byHPRT gene rearrangement
TP Yang, JT Stout, DS Konecki, PI Patel… - Somatic cell and …, 1988 - Springer
TP Yang, JT Stout, DS Konecki, PI Patel, RL Alford, CT Caskey
Somatic cell and molecular genetics, 1988•SpringerMolecular analysis of an unusual patient with the Lesch-Nyhan syndrome has suggested
that the mutation is due to a partial HPRT gene duplication. We now report the cloning and
sequencing of the mutant HPRT cDNA 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 HPRT alleles. Growth of Epstein-Barr …
that the mutation is due to a partial HPRT gene duplication. We now report the cloning and
sequencing of the mutant HPRT cDNA 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 HPRT alleles. Growth of Epstein-Barr …
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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