Abstract Details

Title Investigation of KCNK18 (TRESK) Genetic Variants in Migraine with and without Aura

Topic Headache

Presentation(s) S55 - (-)

Poster/Presentation
Number 003

Objective

Background Migraine is a chronic neurovascular disorder characterized by recurrent headache attacks that, in approximately 25% of cases, are associated with transient focal neurological symptoms (aura). Migraine with and without aura (MA and MO) have a strong genetic basis. Recently, a frameshift mutation (F139Wfsx24) in the KCNK18 gene (10q25.3) was reported in a large multigenerational MA pedigree. KCNK18 gene codes for TRESK, a member of the two-pore domain (K2P) family of potassium channels. The F139Wfsx24 mutation causes a complete loss of TRESK function, suggesting that TRESK dysfunction might play a possible role in migraine pathogenesis.

Design/Methods All three exons and intronic-exonic boundaries of the KCNK18 gene were sequenced in a large group of subjects, including 425 migraine patients (ICHD-II criteria; 255 MA, 170 MO) and 247 healthy controls. In silico analyses were performed using PolyPhen2 and SIFT programs. The clinical characteristics of migraineurs with gene mutations were examined.

Results We identified five genetic variants (G10R, C110R, Y163Y, S231P, F372L) in the coding regions and one genetic variant (c352+24 C>T) in the intronic region of the KCNK18 gene in patients with either MA or MO. Three of these variants have been already published while three are new. In silico analysis suggested a pathogenetic role for two of these variants.

Conclusions Our study confirmed the presence of KCNK18 gene mutations in migraine with aura patients and found gene mutations also in migraine without aura patients. The functional significance of the observed mutations and the effects on TRESK function deserve additional studies.

Authors/Disclosures
Innocenzo Rainero, MD, PhD (University of Turin) PRESENTER	No disclosure on file
Allison Brashear, MD, MBA, FAAN (Univeristy of Buffalo)	Dr. Brashear has received personal compensation for serving as an employee of McKnight Brain Res Found. Dr. Brashear has received personal compensation for serving as an employee of American Board of Psychiatry and Neurology. Dr. Brashear has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for ABPN. Dr. Brashear has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for McKnight Brain Research Foundation i. Dr. Brashear has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Care Directions- start up . Dr. Brashear has stock in Caredirections . The institution of Dr. Brashear has received research support from NINDS. Dr. Brashear has received publishing royalties from a publication relating to health care. Dr. Brashear has received personal compensation in the range of $500-$4,999 for serving as a Special government employee and study section reviewer with NIH. Dr. Brashear has received personal compensation in the range of $0-$499 for serving as a Adminstrative board -travel reimbursement with AAMC.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Lorenzo Pinessi, MD (University of Turin/Dept of Neuroscience)	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��