Genetic complexity of a single-gene disorder
Molecular Therapy, August 2007. 15(8)
On first glance, Lesch-Nyhan’s disease (LND) might appear to be a straightforward disease: A single enzyme of the purine salvage pathway (hypoxanthine phosphoribosyltransferase, HPRT) is missing, resulting in expected increases in uric acid.
However, although biochemical studies have hinted at a role for abnormalities in dopamine metabolism, the precise mechanism underlying the neuropsychiatric phenotype of LND remains elusive.
Song and Friedmann compare the expression of more than 40,000 genes in the brain and liver of wild type and HPRT knockout mice.
Both expected and unexpected changes were found in the expression of a number of genes, revealing the genetic complexity of this supposed single-gene disorder.