Abstract | BACKGROUND: OBJECTIVE: To document a family in which a single HPRT gene mutation has led to 3 different clinical and enzymatic phenotypes. DESIGN: Case report. Settings A university-based outpatient metabolic clinic and a biochemical genetics laboratory. Patients Three males (2 infants and their grandfather) from the same family with Lesch-Nyhan variant, including one of the oldest patients with Lesch-Nyhan variant at diagnosis (65 years). MAIN OUTCOME MEASURES: Clinical and biochemical observations. RESULTS: Sequencing of 5 family members revealed a novel mutation c.550G>T in exon 7 of the HPRT gene. The considerably variable clinical phenotype corresponded with the variable enzymatic activity in the 3 males, with the grandfather being the most severely affected. CONCLUSIONS: The different phenotypes encountered in the enzymatic analysis of cultured fibroblasts from a single mutation in the same family is unprecedented. The significant decrease in the grandfather's HPRT enzymatic activity compared with that of his grandchildren could be a function of the Hayflick Limit Theory of cell senescence.
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Authors | Kyriakie Sarafoglou, Krista Grosse-Redlinger, Christopher J Boys, Laurence Charnas, Noelle Otten, Robyn Broock, William L Nyhan |
Journal | Archives of neurology
(Arch Neurol)
Vol. 67
Issue 6
Pg. 761-4
(Jun 2010)
ISSN: 1538-3687 [Electronic] United States |
PMID | 20558399
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hypoxanthine Phosphoribosyltransferase
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Topics |
- Aged
- Child, Preschool
- DNA Mutational Analysis
- Family Health
- Female
- Humans
- Hypoxanthine Phosphoribosyltransferase
(genetics, metabolism)
- Lesch-Nyhan Syndrome
(genetics, physiopathology)
- Male
- Mutation
(genetics)
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