|
|||||
|
|
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures |
|
| Authors: | Karen N. McFarland Jilin Liu Ivette Landrian Desmond Zeng Salmo Raskin Mariana Moscovich Emilia M. Gatto Adriana Ochoa Hélio A. G. Teive Astrid Rasmussen Tetsuo Ashizawa |
| Affiliation: | 1. Department of Neurology, University of Florida, Gainesville, FL, 32610, USA 2. Evelyn F. & William L. McKnight Brain Institute at the University of Florida, Gainesville, FL, 32610, USA 3. Core for Advanced Molecular Investigation, Graduate Program in Health Sciences, Center for Biological and Health Sciences, University of Paraná, Imaculada Concei??o St 1155 - CCBS/PPGCS, Prado Velho, CEP 80215-901, Curitiba, Paraná, Brazil 4. Movement Disorders Unit, Neurology Service, Hospital de Clínicas, Federal University of Paraná, Centro, Curitiba, Paraná, 80060-150, Brazil 5. Departamento de Neurología, Sanatorio de la Trinidad Mitre, Argentin, Buenos Aires, Argentina 6. Instituto de Neurosciencias Buenos Aires, INEBA, Argentin, 1428, Buenos Aires, Argentina 7. Department of Neurogenetics, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez, Mexico City, DF, Mexico 8. Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA 9. 1149?S Newell Drive, PO Box 200136, Gainesville, FL, 32610, USA |
| Abstract: | Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilepsy. SCA10 expansions containing penta- and heptanucleotide interruption motifs, termed “ATCCT interruptions,” experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic seizures in one Mexican-American SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT interruptions confer a greater risk for developing seizures in these families. Notably, we find that the presence of repeat interruptions within the SCA10 expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in SCA10 repeat expansion indicates a significant risk for the epilepsy phenotype and should be considered during genetic counseling. |
| Keywords: | |
| 本文献已被 SpringerLink 等数据库收录！ | |