NOTCH2NLC Repeat Expansion Testing
Description
Pathogenic GGC repeat expansions in the 5′ untranslated region of the NOTCH2NLC gene have been associated with a spectrum of autosomal dominant neurological diseases including neuronal intranuclear inclusion disease (NIID), oculopharyngodistal myopathy 3 (OPDM3), hereditary essential tremor 6 (ETM6), multiple system atrophy (MSA), and Parkinson’s disease 1. The pathogenic repeat expansions have been shown to lead to the expression of neurotoxic proteins with poly-amino acid tracts 2.
Pathogenicity is dependent upon GGC repeat length according to the following ranges 3-5:
Normal Alleles | Mutable Normal Alleles | Intermediate/Uncertain Alleles | Reduced Penetrance Alleles | Full Penetrance Alleles |
40 or fewer | - | 41-59 | - | 60 or more* |
*Repeat length is correlated with phenotype: Large expansions of >200 are associated with earlier onset and muscle weakness, parkinsonism is typically associated with <100 repeats.
Tests That Analyze NOTCH2NLC Repeats
Additional Resources
Same Symptoms, Different Diagnoses
Five patients ranging in age from 59-70 presented with similar symptoms of progressive cerebellar ataxia, gait imbalance, progressive sensory neuropathy and dysphagia and/or dysarthria. Each received a different diagnosis with Variantyx testing.
