TY - JOUR
T1 - Emerging differences between Huntington's disease-like 2 and Huntington's disease
T2 - A comparison using MRI brain volumetry
AU - Anderson, David G.
AU - Haagensen, Mark
AU - Ferreira-Correia, Aline
AU - Pierson, Ronald
AU - Carr, Jonathan
AU - Krause, Amanda
AU - Margolis, Russell L.
N1 - Funding Information:
Funding was received from The Medical Research Council of South Africa for this study. RLM received support from the ABCD Charitable Trust.
Funding Information:
We wish to thank the Department of Radiology at the University of the Witwatersrand Donald Gordon Medical Centre, Dr. TJ Nel and Partners for generously donating all the MRI scans for this study and all the staff at the Department for their helpfulness and participation. We would also like to acknowledge and thank Marianne Gomes for co-ordinating and counselling the patients and families in this study and Dr. Petra Gaylard for her assistance with the statistical analysis of the data. Most importantly, we would like to thank the patients and their families for their time and kind participation in this study.
Publisher Copyright:
© 2019 The Authors
PY - 2019
Y1 - 2019
N2 - Huntington's Disease-Like 2 (HDL2), caused by a CTG/CAG expansion in JPH3 on chromosome 16q24, is the most common Huntington's Disease (HD) phenocopy in populations with African ancestry. Qualitatively, brain MRIs of HDL2 patients have been indistinguishable from HD. To determine brain regions most affected in HDL2 a cross-sectional study using MRI brain volumetry was undertaken to compare the brains of nine HDL2, 11 HD and nine age matched control participants. Participants were ascertained from the region in South Africa with the world's highest HDL2 incidence. The HDL2 and HD patient groups showed no significant differences with respect to mean age at MRI, disease duration, abnormal triplet repeat length, or age at disease onset. Overall, intracerebral volumes were smaller in both affected groups compared to the control group. Comparing the HDL2 and HD groups across multiple covariates, cortical and subcortical volumes were similar with the exception that the HDL2 thalamic volumes were smaller. Consistent with other similarities between the two diseases, these results indicate a pattern of neurodegeneration in HDL2 that is remarkably similar to HD. However smaller thalamic volumes in HDL2 raises intriguing questions into the pathogenesis of both disorders, and how these volumetric differences relate to their respective phenotypes.
AB - Huntington's Disease-Like 2 (HDL2), caused by a CTG/CAG expansion in JPH3 on chromosome 16q24, is the most common Huntington's Disease (HD) phenocopy in populations with African ancestry. Qualitatively, brain MRIs of HDL2 patients have been indistinguishable from HD. To determine brain regions most affected in HDL2 a cross-sectional study using MRI brain volumetry was undertaken to compare the brains of nine HDL2, 11 HD and nine age matched control participants. Participants were ascertained from the region in South Africa with the world's highest HDL2 incidence. The HDL2 and HD patient groups showed no significant differences with respect to mean age at MRI, disease duration, abnormal triplet repeat length, or age at disease onset. Overall, intracerebral volumes were smaller in both affected groups compared to the control group. Comparing the HDL2 and HD groups across multiple covariates, cortical and subcortical volumes were similar with the exception that the HDL2 thalamic volumes were smaller. Consistent with other similarities between the two diseases, these results indicate a pattern of neurodegeneration in HDL2 that is remarkably similar to HD. However smaller thalamic volumes in HDL2 raises intriguing questions into the pathogenesis of both disorders, and how these volumetric differences relate to their respective phenotypes.
KW - HD-phenocopy
KW - Huntington's Disease
KW - Huntington's Disease-like 2
KW - MRI brain volumetry
KW - Magnetic Resonance Imaging
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U2 - 10.1016/j.nicl.2019.101666
DO - 10.1016/j.nicl.2019.101666
M3 - Article
C2 - 30682531
AN - SCOPUS:85060198544
SN - 2213-1582
VL - 21
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
M1 - 101666
ER -