Dravet syndrome is a severe genetic epilepsy that appears early in life. About 75 percent of cases can be attributed to mutations in the SCN1A gene encoding the sodium channel NaV1.1. The remaining patients with this syndrome are without a definitive molecular genetic diagnosis. Research presented today at the American Epilepsy Society’s 65th Annual Meeting has found a non-SCN1A candidate gene and suggests that Dravet syndrome may be caused by any one of a number of yet unidentified genes.
In order to identify novel candidate genes for Dravet syndrome, investigators from the University of Washington selectively sequenced the protein coding regions of all genes from six non-SCN1A patients. (Platform C.03) Their analysis revealed an unexpected, and previously unidentified de novo SCN1A mutation in one of the patients. Another patient was discovered to carry a de novo, rare mutation in a GABA-receptor gene, GABRA1.
“The GABRA1 gene is an excellent new candidate gene for Dravet syndrome and deserves follow-up in a larger series of patients,” says Heather Mefford, the lead author. “The fact that we did not find mutations in the same genes in the remaining four patients suggests that there are several more genes for Dravet syndrome yet to be discovered.”
Dr. Mefford noted further that the sequencing approach used in the analysis, called whole exome sequencing, is an effective approach in identifying candidate Dravet genes. Whole exome sequencing looks at the protein coding region in the whole human gene pool for mutations that may cause disease.
The investigators will be assessing additional patients for other potential candidate genes for Dravet syndrome.