C9orf72 variant motor neurone disease (MND): investigations

Genetics

• The C9orf72 gene mutation is on chromosome 9p21
• It is a G4C2 (GGGGCC) hexanucleotide repeat expansion disease
• The repeat size correlates with age
• ≥24 repeats may be pathogenic
• It demonstrates genetic anticipation by about 7 years
• The transmission is autosomal dominant

References

1. Hsiung GY, DeJesus-Hernandez M, Feldman HH, et al. Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p. Brain 2012; 135:709-722.
2. Hosler BA, Siddique T, Sapp PC, et al. Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22. JAMA 2000; 284:1664-1669.
3. Vance C, Al-Chalabi A, Ruddy D, et al. Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3. Brain 2006; 129:868-876.
4. van Rheenen W, van Blitterswijk M, Huisman MHB, et al. Hexanucleotide repeat expansions in C9ORF72 in the spectrum of motor neuron diseases. Neurology 2012; 79:878-882.
5. Umoh ME, Fournier C, Li Y, et al. Comparative analysis of C9orf72 and sporadic disease in an ALS clinic population. Neurology 2016; 87:1024-1030. 
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Related checklists

• C9orf72 variant motor neurone disease (MND): clinical features
• Flail arm syndrome (FAS) variant motor neurone disease (MND)
• Mills variant motor neurone disease (MND):
• Madras motor neuron disease (MMND)
• Motor neurone disease (MND): multisystem proteinopathy
• Paraneoplastic motor neurone disease (MND)
• Motor neurone disease (MND): FEWDON variant
• FUS variant motor neurone disease (MND)
• Motor neurone disease (MND): miscellaneous variants