Abstract

Spinocerebellar ataxia type 3 (SCA3), also called Machado-Joseph disease (MJD), is one of the most common SCAs worldwide and caused by a CAG repeat expansion located in ATXN3 gene. Based on the CAG repeat numbers, alleles of ATXN3 can be divided into normal alleles (ANs), intermediate alleles (AIs) and expanded alleles (AEs). It was controversial whether the frequency of large normal alleles (large ANs) is related to the prevalence of SCA3 or not. And there were huge chaos in the comprehension of the specific numbers of the range of CAG repeats which is fundamental for genetic analysis of SCA3. To illustrate these issues, we made a novel CAG repeat ladder to detect CAG repeats of ATXN3 in 1003 unrelated Chinese normal individuals and studied haplotypes defined by three single nucleotide polymorphisms (SNPs) closed to ATXN3. We found that the number of CAG repeats ranged from 13 to 49, among them, 14 was the most common number. Positive skew, the highest frequency of large ANs and 4 AIs which had never been reported before were found. Also, AEs and large ANs shared the same haplotypes defined by the SNPs. Based on these data and other related studies, we presumed that de novo mutations of ATXN3 emerging from large ANs are at least one survival mechanisms of mutational ATXN3 and we can redefine the range of CAG repeats as: ANs≤44, 45 ≤AIs ≤49 and AEs≥50.

Highlights

  • Spinocerebellar ataxias (SCA) were a group of autosomal dominant ataxic disorders and spinocerebellar ataxia type 3 (SCA3) was regarded as one of the most common SCAs in the world [1, 2]

  • SCA3 was caused by a CAG repeat expansion located in exon10 of the ATXN3 gene on chromosome 14q32.1 [3] and it was associated with a variety of clinical manifestations, including progressive ataxia, ophthalmoplegia, pyramidal signs, extrapyramidal signs and facial myokymia [4]

  • The different bands were distinct on polyacrylamide gel (PAGE)

Read more

Summary

Introduction

Spinocerebellar ataxias (SCA) were a group of autosomal dominant ataxic disorders and spinocerebellar ataxia type 3 (SCA3) was regarded as one of the most common SCAs in the world [1, 2]. SCA3 was caused by a CAG repeat expansion located in exon of the ATXN3 gene on chromosome 14q32.1 [3] and it was associated with a variety of clinical manifestations, including progressive ataxia, ophthalmoplegia, pyramidal signs, extrapyramidal signs and facial myokymia [4].

Methods
Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.