Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an agedependent neuropathy.
Submitted By: Ellen Burns, Medical Liaison
The very impressive title is the name of an article published in Human Molecular Genetics, 2005, Vol. 14, No. 22. pages 3507-3521.
The primary author of this publication is Alexander McCampbell, who is responsible for the development of the mouse model for HSN-1. Others whose expertise contributed to the report include Dr. Robert H. Brown, Junior, Director of the Day Laboratory for Neuromuscular Research, Charlestown, Massachusetts and Dr. Teresa M. Dunn, Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Mutations in enzymes involved in sphingolipid metabolism cause a variety of neurological disorders, but how this happens, at the cellular level, is not known.
A mutated gene has been associated with HSN-1. It is identified as SPTLC1. Genes make proteins; proteins make enzymes. SPTLC1 encodes one subunit of the serine palmitoyltransferase enzyme (SPT), the rate-limiting enzyme in sphingolipid synthesis. This enzyme is known to affect the production of a fatty substance (glycosyl ceramide) in the body. HSN-1 patients have reduced SPT activity.
As we know, hereditary sensory and autonomic neuropathy type one (HSN-1) is