Short tandem repeat expansions in LRP12 are absent in familial and sporadic amyotrophic lateral sclerosis patients of European ancestry

In patients of Asian ancestry, a heterozygous CGG repeat expansion of >100 units in LRP12 is the cause of oculopharyngodistal myopathy type 1 (OPDM1), and has been associated with amyotrophic lateral sclerosis (ALS) when repeat lengths are between 61-100 units, although with unusually long disease duration and without significant upper motor neuron involvement. This study investigated if LRP12 CGG tandem repeats were expanded in ALS patients of European ancestry. We screened whole-genome sequencing data from 608 sporadic ALS patients, 35 familial ALS probands, and 4,703 neurologically normal controls for the LRP12 CGG expansion using ExpansionHunter v4. All individuals had LRP12 CGG repeat lengths between 3-25 units. Our results suggest that LRP12 CGG repeat expansions may only be present in ALS patients of Asian ancestry with atypical clinical presentations.