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C9orf72 hexanucleotide repeat expansion found in suspected spinobulbar muscular atrophy (SBMA)
Affiliations- Institute of Psychiatry and Neurology, Warsaw, Poland
- Department of Neurology, Medical University of Warsaw, Poland
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Abstract
Introduction. The expansion of a hexanucleotide GGGGCC repeat (G4C2) in the C9orf72 locus is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In addition, C9orf72 expansion has also been detected in patients with a clinical manifestation of Parkinson’s Disease (PD), Alzheimer’s Disease (AD), Huntington’s Disease (HD), and ataxic disorders.
Material and methods. A total of 1,387 patients with clinically suspected ALS, HD or spinal and bulbar muscular atrophy (SBMA) were enrolled, and the prevalence of C9orf72 expansions was estimated.
Results. The hexanucleotide expansion accounted for 3.7% of the ALS patients, 0.2% of the HD suspected patients with excluded HTT mutation, and 1.3% of the suspected SBMA patients with excluded mutation in AR gene.
Conclusions: This is the first report revealing the presence of C9orf72 expansion in patients with a suspected SBMA diagnosis. Consequently, we advise testing for C9orf72 expansion in patients presenting with the SBMA phenotype and a genetically unsolved diagnosis.
Abstract
Introduction. The expansion of a hexanucleotide GGGGCC repeat (G4C2) in the C9orf72 locus is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In addition, C9orf72 expansion has also been detected in patients with a clinical manifestation of Parkinson’s Disease (PD), Alzheimer’s Disease (AD), Huntington’s Disease (HD), and ataxic disorders.
Material and methods. A total of 1,387 patients with clinically suspected ALS, HD or spinal and bulbar muscular atrophy (SBMA) were enrolled, and the prevalence of C9orf72 expansions was estimated.
Results. The hexanucleotide expansion accounted for 3.7% of the ALS patients, 0.2% of the HD suspected patients with excluded HTT mutation, and 1.3% of the suspected SBMA patients with excluded mutation in AR gene.
Conclusions: This is the first report revealing the presence of C9orf72 expansion in patients with a suspected SBMA diagnosis. Consequently, we advise testing for C9orf72 expansion in patients presenting with the SBMA phenotype and a genetically unsolved diagnosis.
Keywords
ALS, C9orf72 locus, dynamic mutation, FTD, microsatellite repeats expansion, SBMA
About this articleTitle
C9orf72 hexanucleotide repeat expansion found in suspected spinobulbar muscular atrophy (SBMA)
Journal
Neurologia i Neurochirurgia Polska
Issue
Article type
Short Communication
Pages
276-280
Published online
2022-06-03
Page views
4646
Article views/downloads
712
DOI
Pubmed
Bibliographic record
Neurol Neurochir Pol 2022;56(3):276-280.
Keywords
ALS
C9orf72 locus
dynamic mutation
FTD
microsatellite repeats expansion
SBMA
Authors
Wiktoria Radziwonik
Ewelina Elert-Dobkowska
Filip Tomczuk
Aleksandra Wozniak
Anna Sobanska
Iwona Stepniak
Dariusz Koziorowski
Jacek Zaremba
Anna Sułek
References (15)- DeJesus-Hernandez M, Mackenzie IR, Boeve BF, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. 2011; 72(2): 245–256.
- Renton AE, Majounie E, Waite A, et al. ITALSGEN Consortium. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011; 72(2): 257–268.
- Chiò A, Borghero G, Pugliatti M, et al. Italian Amyotrophic Lateral Sclerosis Genetic (ITALSGEN) Consortium. Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene. Arch Neurol. 2011; 68(5): 594–598.
- Zou ZY, Zhou ZR, Che CH, et al. Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2017; 88(7): 540–549.
- Liu Y, Yu JT, Zong Yu, et al. C9ORF72 mutations in neurodegenerative diseases. Mol Neurobiol. 2014; 49(1): 386–398.
- Millecamps S, Boillée S, Le Ber I, et al. Phenotype difference between ALS patients with expanded repeats in C9ORF72 and patients with mutations in other ALS-related genes. J Med Genet. 2012; 49(4): 258–263.
- Beck J, Poulter M, Hensman D, et al. Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK population. Am J Hum Genet. 2013; 92(3): 345–353.
- Burrell J, Halliday G, Kril J, et al. The frontotemporal dementia-motor neuron disease continuum. The Lancet. 2016; 388(10047): 919–931.
- Figueroa KP, Gan SR, Perlman S, et al. C9orf72 repeat expansions as genetic modifiers for depression in spinocerebellar ataxias. Mov Disord. 2018; 33(3): 497–498.
- Hensman Moss DJ, Poulter M, Beck J, et al. C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies. Neurology. 2014; 82(4): 292–299.
- Ida CM, Butz ML, Lundquist PA, et al. C9orf72 Repeat Expansion Frequency among Patients with Huntington Disease Genetic Testing. Neurodegener Dis. 2018; 18(5-6): 239–253.
- Fahey C, Byrne S, McLaughlin R, et al. Analysis of the hexanucleotide repeat expansion and founder haplotype at C9ORF72 in an Irish psychosis case-control sample. Neurobiol Aging. 2014; 35(6): 1510.e1–1510.e5.
- Hsiao CT, Tsai PC, Liao YC, et al. C9ORF72 repeat expansion is not a significant cause of late onset cerebellar ataxia syndrome. J Neurol Sci. 2014; 347(1-2): 322–324.
- Martins J, Damásio J, Mendes A, et al. Clinical spectrum of C9orf72 expansion in a cohort of Huntington's disease phenocopies. Neurol Sci. 2018; 39(4): 741–744.
- Alva-Diaz C, Alarcon-Ruiz CA, Pacheco-Barrios K, et al. Hexanucleotide Repeat in Huntington-Like Patients: Systematic Review and Meta-Analysis. Front Genet. 2020; 11: 551780.
