The Medical Biochemistry Laboratory is exploring the role of the HSD17B10 gene in intellectual disability. The human HSD17B10 gene product, hydroxysteroid (17-beta) dehydrogenase type 10 (HSD10), plays a pivotal role in several different metabolic pathways and contributes to normal cognitive development. Some families with X-linked intellectual disability have been found to have loss-of-function mutations or aberrant expression of the HSD17B10 gene. Elucidation of the molecular mechanism underlying abnormalities in this gene that result in intellectual disability is a prerequisite for the development of effective treatment and prevention of many developmental disabilities.
Our current projects are addressing:
- Regulation of human HSD17B10 gene expression: The over-expression of HSD17B10 gene and high copy numbers of this gene are an important genetic cause of developmental disabilities.
- Mitochondrial dysfunction due to abnormalities of HSD17B10 gene: Mitochondrial dysfunction is prominent in individuals with intellectual disability who have HSD10 deficiency. In this project, we are seeking evidence that HSD10 is essential to the metabolism of allopregnanolone and other neuroactive steroids in neurons and glia and ways to alter the amount of HSD10 as well as its activity in mitochondria. Success in this project is expected to create a new approach to ameliorate cognitive impairment in individuals with intellectual disability and HSD10 deficiency and to prevent some cases of developmental disabilities.