Evaluation of SCN8A as a candidate gene for autosomal dominant essential tremor.
OBJECTIVE
Essential tremor (ET) is a common inherited movement disorder whose causes remain unknown. The presence of spontaneous tremor in murine mutants may provide clues into the pathogenesis of ET. SCN8A encodes the neuronal voltage gated sodium channel Na(v)1.6 that is widely expressed in the central nervous system. Several mutations of Scn8a in the mouse result in congenital postural tremor of the extremities and head.


METHODS
We screened SCN8A as a candidate gene in a cohort of 95 Caucasian patients with ET and a positive family history, including 48 patients with early onset in the first two decades of life. Early and adult onset ET subgroups did not differ in disease severity, but early onset patients had longer disease duration. Observed sequence variants were also screened in an ethnically matched control group.


RESULTS
We did not detect SCN8A mutations affecting amino acid sequence or splice sites in our cohort of ET patients.


CONCLUSIONS
Although mutations of Scn8a cause congenital tremor in mice, mutations in the sequence of the exons and splice sites of human SCN8A do not appear to be a common cause of autosomal dominant essential tremor in Caucasian patients.
Sharkey
Lisa M
LM
Department of Human Genetics, University of Michigan, 4812 Med Sci. II, 1241 Catherine Street, Ann Arbor, MI 48109-5618, USA. lisams@umich.edu
Jones
Julie M
JM
Hedera
Peter
P
Meisler
Miriam H
MH
D000328:Adult; D000368:Aged; D002170:Canada; D004252:DNA Mutational Analysis; D020329:Essential Tremor / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*
D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C100681:SCN8A protein, human; D015222:Sodium Channels