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:
Normal Alleles | Mutable Normal Alleles | Intermediate/Uncertain Alleles | Reduced Penetrance Alleles | Full Penetrance Alleles |
24 or fewer | - | 25-60 | - | 61 or more |
Note: As FTD/ALS1 is typically adult onset, C9orf72 repeat expansions are not reported in minors in comprehensive analyses.
Tests That Analyze C9orf72 Repeats
- Genomic Unity® 2.0
- Genomic Unity® Whole Genome Analysis
- Genomic Unity® Lightning Genome Analysis – Standard
- Genomic Unity® Exome Plus Analysis
- Genomic Unity® Exome Analysis
- Genomic Unity® Movement Disorders Analysis
- Genomic Unity® Motor Neuron Disorders Analysis
- Genomic Unity® Dementia Analysis
- Genomic Inform®
Additional Resources
Missed By Others, Found By Us
A 54-year-old male with a family history of ALS and dementia presented with symptoms of ataxia. Variantyx testing identified a heterozygous, pathogenic GGGGCC repeat expansion in the C9orf72 gene. Long-read sequencing confirmed and sized the expanded allele as ~1,600 repeats.
