ExpansionHunter genotypes are remarkably accurate for both genomes and exomes at the EP400 locus. If you would like to genotype your sample(s), please use the locus definition @ github.com/broadinstitu...

Now, this analysis of 1027 long read AoU genomes has shown that 70% of known disease-associated STR loci are among the top 1% of the most variable STR loci in the genome. Although it wasn't yet a known locus, the EP400 STR also clustered among that top 1%. [5/N]

Since then, we have genotyped many thousands of other cases and over 1/2 million controls (UKBB, gnomAD, AoU) but haven't found any other samples with more than 50 repeats at this locus, so expansions are extremely rare. [4/N]

We consider this expansion, found in both affected members of a single family, to be the most likely cause of their spinocerebellar ataxia. [3/N]

Back in 2022, by genotyping ~5 million STR loci in thousands of short-read rare disease genomes using ExpansionHunter and GangSTR, we discovered an unusually large (≥55 repeats) heterozygous coding CAG expansion in exon #47 of the EP400 gene. [2/N]

It was great to be able to contribute the EP400 finding to this preprint. Together with @ginaravenscroft.bsky.social and @cfolland.bsky.social we flagged a novel CAG repeat locus in the EP400 gene as a likely (though extremely rare) cause of spinocerebellar ataxia when expanded to ≥55 repeats. [1/N]