The role of C9orf72 in neurodegenerative disorders: a systematic review, an updated meta-analysis, and the creation of an online database

Marogianni, Chrysoula; Rikos, Dimitrios; Provatas, Antonios; Dadouli, Katerina; Ntellas, Panagiotis; Tsitsi, Panagiota; Patrinos, George P.; Dardiotis, Efthimios; Hadjigeorgiou, George; Xiromerisiou, Georgia

doi:10.1016/j.neurobiolaging.2019.04.012

Cited by 29 publications

(28 citation statements)

References 24 publications

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“…Two additional studies were identified through other sources. Then, after the full-text review, seven studies were excluded (Beck et al, 2013 ; Hensman Moss et al, 2014b ; Abramycheva et al, 2015 ; Dolzhenko et al, 2017 ; Kartanou et al, 2017 ; Martins et al, 2018b ; Marogianni et al, 2019 ) ( Supplementary Table 1 ). Finally, 10 studies were included in the meta-analysis (Hensman Moss et al, 2014a ; Kostic et al, 2014 ; Koutsis et al, 2015 ; Fedotova et al, 2016 ; Mariani et al, 2016 ; Baine et al, 2018 ; Ida et al, 2018 ; Martins et al, 2018a , b ; Kaur et al, 2020 ; Rikos et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…Previous systematic reviews found a 1.6 and 2% prevalence of C9orf72 repeat expansion in HLD patients (Marogianni et al, 2019;Rikos et al, 2020). However, we strictly followed PRISMA guidelines for systematic reviews and analyzed cases with intermediate alleles (<30 repeat range), which are cataloged as unclear clinical significance (Fedotova et al, 2016;Ida et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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C9orf72 Hexanucleotide Repeat in Huntington-Like Patients: Systematic Review and Meta-Analysis

et al. 2020

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Introduction: Patients with Huntington-Like disorders (HLD) comprise a variety of allelic disorders sharing a Huntington phenotype. The hexanucleotide repeat expansion of the C9orf72 gene could explain part of the HLD etiology. We aimed to conduct a systematic review and meta-analysis looking for the frequency of the hexanucleotide repeat expansion of the C9orf72 gene in HLD patients. Methods: The protocol was registered on the International Prospective Register of Systematic Reviews database (PROSPERO) (registration number: CRD42018105465). The search was carried out in Medline, Scopus, Web of Science, and Embase in April 2018, and updated in July 2020. Observational studies reporting patients with HLD carrying the hexanucleotide repeat expansion in the C9orf72 gene were selected and reviewed; this process was duplicated. The cutoff threshold for considering the hexanucleotide expansion as a pathogenic variant was equal to or >30 G 4 C 2 repeats. Cases with intermediate alleles with 20-29 repeat are also analyzed. Pooled frequency and 95% CI were calculated using random-effects models. Results: Nine out of 219 studies were selected, reporting 1,123 affected individuals with HLD. Among them, 18 individuals carried C9orf72 expansion, representing 1% (95% CI: 0-2%, I 2 = 0%) of the pooled frequency. Seven selected studies came from European centers, one was reported at a US center, and one came from a South-African center. We identified five individuals carrying intermediate alleles representing 3% (95% CI: 0-14%, I 2 = 78.5%). Conclusions: The frequency of C9orf72 unstable hexanucleotide repeat expansion in HLD patients is very low. Further studies with more accurate clinical data and from different ethnic backgrounds are needed to confirm this observation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C9orf72 Hexanucleotide Repeat in Huntington-Like Patients: Systematic Review and Meta-Analysis

et al. 2020

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“…In the meta-analysis, the majority of the studies included Caucasian patients and only one included Afro-Americans, in which no positive patients were found. Based also in the frequency of C9orf72 expansion in ALS/FTD cohorts, an ethnicity predilection distinguishes [5]. This fact could help the clinicians prioritize the genetic tests performed to their patients.…”

Section: Discussionmentioning

confidence: 97%

“…The design of the database was described previously in detail [5]. The web database can be accessed via the following link https://neurodegenerative.herokuapp.com/.…”

Section: Search Strategy Study Selection and Data Extractionmentioning

confidence: 99%

“…A recent and promising scientific discovery was the identification of a mutation in the C9orf72 gene. This mutation was identified as the most common genetic cause of both familial and sporadic ALS and FTD in Caucasians [5]. In the non-coding region of C9orf72 gene, a polymorphic GGGGCC hexanucleotide repeat was found, that was detected in controls only in a few copies (less than 23 repeats), whereas in patients suffering from ALS and FTLD it was found in at least a few hundred (estimated around 700-1600) [6].…”

Section: Introductionmentioning

confidence: 99%

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Screening for the C9ORF72 Expansion in Greek Huntington Disease Phenocopies and Controls and Meta-analysis of Current Data

Rikos

Marogianni

Provatas

et al. 2020

Tremor and Other Hyperkinetic Movements

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Huntington-disease like disorders (HDL) are a rare cause of chorea, resembling Huntington's disease (HD) and its common triplet of symptoms-chorea, cognitive decline, and psychiatric symptoms, but lack the CAG expansion, responsible for the original disorder. Huntington's disease phenocopy syndromes, represent about 1% of the cases with a clinical suspicion of HD [3]. Several neurogenetic diseases are

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Resting‐state fMRI functional connectome of C9orf72 mutation status

Stanziano,

Fedeli,

Manera

et al. 2024

Ann Clin Transl Neurol

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ObjectiveThe resting‐state functional connectome has not been extensively investigated in amyotrophic lateral sclerosis (ALS) spectrum disease, in particular in relationship with patients' genetic status.MethodsHere we studied the network‐to‐network connectivity of 19 ALS patients carrying the C9orf72 hexanucleotide repeat expansion (C9orf72+), 19 ALS patients not affected by C9orf72 mutation (C9orf72−), and 19 ALS‐mimic patients (ALSm) well‐matched for demographic and clinical variables.ResultsWhen compared with ALSm, we observed greater connectivity of the default mode and frontoparietal networks with the visual network for C9orf72+ patients (P = 0.001). Moreover, the whole‐connectome showed greater node degree (P < 0.001), while sensorimotor cortices resulted isolated in C9orf72+.InterpretationOur results suggest a crucial involvement of extra‐motor functions in ALS spectrum disease. In particular, alterations of the visual cortex may have a pathogenic role in C9orf72‐related ALS. The prominent feature of these patients would be increased visual system connectivity with the networks responsible of the functional balance between internal and external attention.

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The role of C9orf72 in neurodegenerative disorders: a systematic review, an updated meta-analysis, and the creation of an online database

Cited by 29 publications

References 24 publications

C9orf72 Hexanucleotide Repeat in Huntington-Like Patients: Systematic Review and Meta-Analysis

C9orf72 Hexanucleotide Repeat in Huntington-Like Patients: Systematic Review and Meta-Analysis

Screening for the C9ORF72 Expansion in Greek Huntington Disease Phenocopies and Controls and Meta-analysis of Current Data

Resting‐state fMRI functional connectome of C9orf72 mutation status

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