Screening for the C9ORF72 expansion in Greek Huntington Disease phenocopies and controls and meta-analysis of current data

Dimitrios Rikos; Chrysoula Marogianni; Antonios Provatas; Thomas Bourinaris; Marianthi Arnaoutoglou; Pantelis Stathis; George P Patrinos; Efthimios Dardiotis; George M Hadjigeorgiou; Georgia Xiromerisiou

doi:10.5334/tohm.61

Screening for the C9ORF72 expansion in Greek Huntington Disease phenocopies and controls and meta-analysis of current data

Tremor Other Hyperkinet Mov (N Y). 2020 Jun 12:10:5. doi: 10.5334/tohm.61.

Affiliations

¹ University of Thessaly, University Hospital of Larissa, Neurology Department, Larissa, GR.
² Department of Molecular Neuroscience Institute of Neurology, University College London, London, UK.
³ First Neurology Clinic, AHEPA Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, GR.
⁴ Department of Neurology, Mediterraneo Hospital, Athens, GR.
⁵ University of Patras School of Health Sciences, Department of Pharmacy, Patras, GR.
⁶ United Arab Emirates University, College of Medicine and Health Sciences, Department of Pathology, Al-Ain, AE.
⁷ United Arab Emirates University, Zayed Center of Health Sciences, Al-Ain, AE.
⁸ Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, GR.
⁹ Department of Neurology, Medical School, University of Cyprus, Nicosia, CY.

PMID: 32775019
PMCID: PMC7394208
DOI: 10.5334/tohm.61

Abstract

Background: Several European studies examined the role of C9orf72 repeat expansion in patients with Huntington-disease like phenotypes (HD-L). The scope of our study is to investigate the expansion frequency in a Greek HD-L cohort and the meta-analysis of all published cases. This will be of use in genetic counseling of these cases.

Methods: A cohort of 74 patients with HD-L and 67 healthy controls were screened for the C9orf72 expansion status. Case-controls comparison was assessed with the Pearson's chi-square statistic for a 2 × 2 table.A systematic database search was conducted and seven studies, including the current study, were considered eligible for inclusion in a meta-analysis considering a total of 812 patients with HD phenocopies. Pooled mutation frequency was calculated using a Random Effects model or the Mantel-Haezsel fixed effects model, depending on the observed heterogeneity.

Results: In our cohort, one patient was found to have a pathologic expansion of C9orf72, and none from the control group (chi-square: 0.91, p-value: 0.34). Pooled mutation frequency was found at 2% (CI: 1-3%) with low heterogeneity (I²:15%).

Discussion: Based on this meta-analysis the recommendation for genetic testing for C9orf72 expansions is further solidified.

Keywords: C9orf72; HD-like phenocopies; Huntington disease; meta-analysis.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

C9orf72 Protein / genetics*
Case-Control Studies
DNA Repeat Expansion
Female
Genetic Testing
Greece
Heredodegenerative Disorders, Nervous System / diagnosis
Heredodegenerative Disorders, Nervous System / genetics*
Humans
Male
Middle Aged

Substances

C9orf72 Protein

Supplementary concepts

Huntington Disease-Like Syndrome

Grants and funding

The study was partly sponsored by the research protocol Analysis of patient cohort at Neurological Department of University Hospital of Larissa for suspects of Niemann Pick Type C retrospectively and prospectively. All authors declare that no relevant financial disclosures exist.