Genetic Variants Associated with Episodic Ataxia in Korea. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Choi, Kwang-Dong; Kim, Ji-Soo; Kim, Hyo-Jung; Jung, Ileok; Jeong, Seong-Hae; Lee, Seung-Han; Kim, Dong; Kim, Sang-Ho; Choi, Seo; Shin, Jin-Hong; Kim, Dae-Seong; Park, Kyung-Pil; Kim, Hyang-Sook; Choi, Jae-Hwan
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 11
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-14254-7
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract Episodic ataxia (EA) is a rare neurological condition characterized by recurrent spells of truncal ataxia and incoordination. Five genes (KCNA1, CACNA1A, CACNB4, SLC1A3, andUBR4 ) have been linked to EA. Despite extensive efforts to genetically diagnose EA, many patients remain still undiagnosed. Whole-exome sequencing was carried out in 39 Korean patients with EA to identify pathogenic mutations of the five known EA genes. We also evaluated 40 candidate genes that cause EA as a secondary phenotype or cerebellar ataxia. Eighteen patients (46%) revealed genetic information useful for establishing a molecular diagnosis of EA. In 11 patients, 16 pathogenic mutations were detected in three EA genes. These included nine mutations inCACNA1A, three inSLC1A3, and four inUBR4 . Three patients had mutations in two genes, eitherCACNA1A andSLC1A3 orCACNA1A andUBR4, suggesting thatSLC1A3 andUBR4 may act as genetic modifiers with synergic effects on the abnormal presynaptic activity caused byCACNA1A mutations. In seven patients with negative results for screening of EA genes, potential pathogenic mutations were identified in the candidate genesATP1A2, SCN1A, TTBK2, TGM6, FGF14, andKCND3 . This study demonstrates the genetic heterogeneity of Korean EA, and indicates that whole-exome sequencing may be useful for molecular genetic diagnosis of EA.