Age-dependent somatic expansion of the ATXN3 CAG repeat in the blood and buccal swab DNA of individuals with spinocerebellar ataxia type 3/Machado-Joseph disease.

ABSTRACT: Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is caused by the expansion of a genetically unstable polyglutamine-encoding CAG repeat in ATXN3. Longer alleles are generally associated with earlier onset and frequent intergenerational expansions mediate the anticipation observed in this disorder. Somatic expansion of the repeat has also been implicated in disease onset and slowing the rate of somatic expansion has been proposed as a therapeutic strategy. Here, we utilised high-throughput ultra-deep MiSeq amplicon sequencing to precisely define the number and sequence of the ATXN3 repeat, the genotype of an adjacent single nucleotide variant and quantify somatic expansion in blood and buccal swab DNA of a cohort of individuals with SCA3 from the Azores islands (Portugal). We

SUBMITTER: Sidky AM 

PROVIDER: S-EPMC11522074 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature