C9orf72 Repeat Expansion Testing

Description

Pathogenic GGGGCC repeat expansions in the C9orf72 gene have been associated with frontotemporal dementia and/or amyotrophic lateral sclerosis (FTD/ALS1). The pathogenic repeat expansions may lead to cellular dysfunction and neurodegeneration through multiple mechanisms including: RNA toxicity from the sequestration of RNA-binding proteins and the subsequent formation of nuclear RNA foci, translated repeat expansions that lead to protein aggregates, and C9orf72 haploinsufficiency.

Pathogenicity is dependent upon GGGGCC repeat length according to the following ranges ^1-2:

Note: As FTD/ALS1 is typically adult onset, C9orf72 repeat expansions are not reported in minors in comprehensive analyses.