Neurodegenerative Diseases

Ramírez-García M.Á.a,b· Dávila-Ortiz de Montellano D.J.a· Martínez-Ruano L.a· Ochoa-Morales A.a· Romero-Hidalgo S.c· Zenteno J.C.d,e· Yescas-Gómez P.a

Author affiliations

aGenetics Department, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, Mexico
bDoctoral Program in Medical Sciences, National Autonomous University of Mexico, Mexico City, Mexico
cComputational Genetics, National Institute of Genomic Medicine, Mexico City, Mexico
dResearch Unit-Genetics Department, Institute of Ophthalmology, “Conde de Valenciana”, Mexico City, Mexico
eDepartment of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico

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Article / Publication Details

First-Page Preview

Received: January 11, 2022
Accepted: July 21, 2022
Published online: August 04, 2022

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

Abstract

Introduction: There are reports of different clinical statuses in carriers of intermediate alleles (IAs) of CAG trinucleotide repeats in the HTT gene, from individuals affected by a clinical picture indistinguishable from Huntington’s disease (HD) to those without manifestations. Therefore, the possible clinical significance of these alleles has been widely debated. Objectives: The aim of this study was to describe general and clinical features and discard HD phenocopies by molecular assessment in a case series of IA carriers on the HTT gene of a laboratory sample from a neurological center in Mexico. Methods: We selected individuals who had previously been tested for the HTT gene expansion, which resulted in IAs. Clinical information was obtained from medical records, and molecular analysis of the JPH3, PRNP, and TBP genes was performed only in IA carriers with clinical manifestations. In addition, two patients with IA and acanthocytes were evaluated by whole-exome sequencing. The scientific and ethical committees of the National Institute of Neurology and Neurosurgery Manuel Velasco Suárez (NINNMVS) approved this study. Results: From 1994 to 2019, the Genetics Department of the NINNMVS confirmed 34 individuals with IAs, 15 of whom belonged to 11 families with HD (IA-HD) and 19 of whom had no family history of HD (IA-non-HD). We found a high proportion of manifestations of the HD phenotypic spectrum in the IA-non-HD subgroup. In addition, among the 20 samples of IA carriers with manifestations molecularly evaluated, we identified two unrelated subjects with CAG/CTG repeat expansions on the JPH3 gene, confirming HD-like 2 (HDL2), and one patient with the homozygous pathogenic c.3232G>T variant (p.Glu1078Ter) in the VPS13A gene, demonstrating choreoacanthocytosis. Discussion/Conclusion: Our results show the most extensive series of subjects with IAs and clinical manifestations. In addition, we identify three HD phenocopies, two HDL2 cases, and one choreoacanthocytosis case. Therefore, we emphasize evaluating other HD phenocopies in IA carriers with clinical manifestations whose family background is not associated with HD.

© 2022 S. Karger AG, Basel

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First-Page Preview

Received: January 11, 2022
Accepted: July 21, 2022
Published online: August 04, 2022

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: https://www.karger.com/NDD

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