Oligogenic variants in NEK1 and ATXN2 in amyotrophic lateral sclerosis: report of two cases and review of the literature.
Émy Roy, Mathieu Blais, Patrick Dion et al.
✦ AI-curated · Sources linked
Case in brief
Two siblings with amyotrophic lateral sclerosis (ALS) were found to carry both a heterozygous ATXN2 32 CAG repeat expansion and a novel heterozygous NEK1 c.1674_1677dup variant. In a large family with thirteen siblings, segregation of both variants was reported. The authors considered this pattern supportive of a possible oligogenic contribution to ALS susceptibility, while noting that the variants’ pathogenic roles remain uncertain.
What made this case unusual
Both affected siblings carried variants in two ALS-associated genes, raising the possibility of an oligogenic rather than single-variant contribution.
Diagnostic / clinical pearl
When interpreting ALS genetic findings, consider that variants of uncertain pathogenicity may occur together; family segregation can inform, but does not establish, their contribution to disease.