Lack of variation of ATTCT pentanucleotide repeats at ATXN10 gene between clinically diagnosed ataxia patients and normal individuals originated from Chinese Han

摘要

The autosomal dominant spinocerebellar ataxias (SCA) are clinically and genetically heterogeneous group of debilitating neurodegenerative diseases characterized by a generalized incoordination of gait, speech and limb movements (Tang et al. 2000; Soong and Paulson 2007). To date, sixteen different genes related to SCA have been identified: ATXN1, ATXN2, MJD1, PLEKHG4, SPTBN2, CACNA1A, ATXN7, ATXN8OS, ATXN10, TTBK2, PPP2R2B, KCNC3, PRKCG, TBP, FGF14 and DRPLA (dentatorubral-pallidoluysian atrophy) (Soong and Paulson 2007). Most subtypes of SCA are caused by unstable CAG repeat expansions encoding polyglutamine tracts, while SCA10 is the only subtype caused by an intronic ATTCT pentanucleotide repeat expansion (Matsuura et al. 2006). Zu et al. (1999) first mapped the SCA10 locus to chromosome 22q13-qter and thereafter cloned the causative gene ATXN10. The expansion of pentanucleotide (ATTCT) repeat is located in intron 9 of the ATXN10 gene (Zu et al. 1999; Matsuura et al. 2000). In SCA10, normal alleles carry 10C22 ATTCT repeats, intermediate alleles with reduced or no penetrance range from 280 to 370 ATTCT repeats, and pathological alleles contain 800C4500 ATTCT repeats (Alonso et al. 2006).