Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS.
Tess D PottingerJoshua E MotelowGundula PovysilCristiane de Araújo Martins MorenoZhong RenHemali Phatnaninull nullTimothy J AitmanJavier Santoyo-Lopeznull nullnull nullDavid B GoldsteinMatthew B HarmsPublished in: medRxiv : the preprint server for health sciences (2023)
Rare genetic variants have been previously associated with amyotrophic lateral sclerosis (ALS). In a large multi-ethnic cohort of 6,970 ALS patients, rare variant burden testing validated known ALS genes and demonstrated the utility of intolerant domain-based collapsing methods. A first- ever analysis in 166 patients with primary lateral sclerosis (PLS), a motor neuron disease related to ALS, found a candidate association to loss-of-function mutations in ANTXR2 .