Pentanucleotide repeats at the spinocerebellar ataxia type 31 (SCA31) locus in Caucasians

Abstract

Spinocerebellar ataxia type 31 (SCA31) was recently discovered to be caused by 2.5- to 3.8-kb-long complex pentanucleotide repeats containing (TGGAA)n, (TAGAA)n, and (TAAAA)n in an intronic region shared by 2 different genes, BEAN (brain expressed, associated with Nedd4) and TK2 (thymidine kinase 2), in chromosome 16q22.1.1,2 Among the 3 pentanucleotide repeats, (TGGAA)n was the only one in which large repeats segregated with the phenotype, suggesting its importance in pathogenesis.2 SCA31 is considered one of a growing number of neuromuscular diseases with RNA-mediated gain-of-function mechanism such as myotonic dystrophies type 1 and 2, SCA8, SCA10, and fragile X–tremor ataxia syndrome.3 While SCA31 is one of the most common SCAs in Japan, it is not known whether it is prevalent in Caucasians. In this study, we directly tested the SCA31 mutation in large European cohorts of SCA families. ### Methods. French and German cohorts of SCA index patients without known mutations were analyzed. The French cohort (n = 271 patients) was collected through a national ataxia network, and the German cohort (n = 49 patients) was collected at the Ludwig-Maximilians-University Munich, Germany. Healthy controls comprising 285 French and 303 German individuals were also tested. The SCA31 locus and its nearby markers were analyzed as previously described.2 #### Standard protocol approvals, registrations, and patient consents. This study was approved by the respective institutional review boards. ### Results. One out of 49 German and 31 out of 271 French SCA index patients carried abnormal expansions (figure,A). Two of these patients carried expansions homozygously. DNA sequencing revealed that the expansions were located at the same position as in Japanese …