Spinocerebellar ataxia type 10 (SCA10) is a rare autosomal-dominant disorder caused by an expanded intronic pentanucleotide repeat in the ATXN10 gene. This repeat expansion when fully penetrant can be typically expected between 850 and 4500 repeats or 4.25 to 22.5 kb. Current diagnostic assays using PCR-based methods or Southern blotting cannot accurately size or resolve the genomic structure of the ATXN10 repeat. In this talk, Dr. Birgitt Schuele elaborates that CRISPR-Cas9 enrichment/single molecule real time (SMRT) sequencing technology and optical mapping now allow for accurate sizing of the repeat expansion, repeat composition, and can resolve somatic mosaicism, which are critical for clinical practice and genetic counseling as variation in the repeat can affect disease penetrance, symptoms, and consequently disease trajectory.
June 15, 2021 | Presentation