TY - JOUR
T1 - C9orf72 Hexanucleotide Repeat in Huntington-Like Patients
T2 - Systematic Review and Meta-Analysis
AU - Alva-Diaz, Carlos
AU - Alarcon-Ruiz, Christoper A.
AU - Pacheco-Barrios, Kevin
AU - Mori, Nicanor
AU - Pacheco-Mendoza, Josmel
AU - Traynor, Bryan J.
AU - Rivera-Valdivia, Andrea
AU - Lertwilaiwittaya, Pongtawat
AU - Bird, Thomas D.
AU - Cornejo-Olivas, Mario
N1 - Funding Information:
This work was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (Z01-AG000949-02). Research reported in this publication was partially supported by the Fogarty International Center (FIC) of the NIH and NINDS (D43TW009345 and D43TW009137).
Publisher Copyright:
© Copyright © 2020 Alva-Diaz, Alarcon-Ruiz, Pacheco-Barrios, Mori, Pacheco-Mendoza, Traynor, Rivera-Valdivia, Lertwilaiwittaya, Bird and Cornejo-Olivas.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/2
Y1 - 2020/11/2
N2 - 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 G4C2 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%, I2 = 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%, I2 = 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.
AB - 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 G4C2 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%, I2 = 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%, I2 = 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.
KW - C9orf72
KW - chorea
KW - Huntington like disorders
KW - prevalence studies
KW - systematic review
UR - http://www.scopus.com/inward/record.url?scp=85096170056&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/06569bef-35fd-3826-a5f1-a4f2f1cf6e39/
U2 - 10.3389/fgene.2020.551780
DO - 10.3389/fgene.2020.551780
M3 - Artículo
C2 - 33240313
AN - SCOPUS:85096170056
SN - 1664-8021
VL - 11
SP - 551780
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 551780
ER -