Clinical spectrum of C9orf72 expansion in a cohort of Huntington’s disease phenocopies
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The expansion in the C9orf72 gene has been recently reported as a genetic cause of Huntington’s disease (HD) phenocopies. We aim to assess the frequency of the C9orf72 gene expansion in a Portuguese HD phenocopies cohort. Twenty HD phenotype-like patients without diagnosis were identified in our institutional database. C9orf72 gene expansion was detected using repeat-primed PCR. Clinical files were reviewed to characterize the phenotype of expansion-positive cases. One patient (5%) was positive for the C9orf72 expansion. A second patient presented 27 repeats—within the intermediate size interval. Both had familial neuropsychiatric disease characterized by diverse movement disorders, dementia, and psychiatric dysfunction that was distinct in severity and clinical expression. C9orf72 disease is clinically heterogeneous and without evident imaging markers. The definition of the role of intermediate alleles and of the pathological threshold for C9orf72 repeat expansions may have diagnostic implications.
KeywordsMovement disorders C9orf72 expansion Huntington’s disease phenocopies Intermediate allele
The authors would like to acknowledge the patients and their family for the participation in this study.
Compliance with ethical standards
Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Kremer B, Goldberg P, Andrew SE, Theilmann J, Telenius H, Zeisler J, Squitieri F, Lin B, Bassett A, Almqvist E, Bird TD, Hayden MR (1994) A worldwide study of the Huntington’s disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 330(20):1401–1406. https://doi.org/10.1056/NEJM199405193302001 CrossRefPubMedGoogle Scholar
- 8.Hensman Moss DJ, Poulter M, Beck J, Hehir J, Polke JM, Campbell T, Adamson G, Mudanohwo E, McColgan P, Haworth A, Wild EJ, Sweeney MG, Houlden H, Mead S, Tabrizi SJ (2014) C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies. Neurology 82(4):292–299. https://doi.org/10.1212/WNL.0000000000000061 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Koutsis G, Karadima G, Kartanou C, Kladi A, Panas M (2015) C9ORF72 hexanucleotide repeat expansions are a frequent cause of Huntington disease phenocopies in the Greek population. Neurobiol Aging 36(1):547.e13–547.e16. https://doi.org/10.1016/j.neurobiolaging.2014.08.020 CrossRefGoogle Scholar
- 11.Schottlaender LV, Polke JM, Ling H et al (2015) Analysis of C9orf72 repeat expansions in a large series of clinically and pathologically diagnosed cases with atypical parkinsonism. Neurobiol Aging 36:1221.e1-6. https://doi.org/10.1016/j.neurobiolaging.2014.08.024 CrossRefPubMedGoogle Scholar
- 12.(2017) Oral sessions. Eur J Neurol 24:19–122. https://doi.org/10.1111/ene.13366