Evaluation of AQP4 functional variants and its association with fragile X-associated tremor/ataxia syndrome
Elias-Mas, Andrea (Universitat de Barcelona)
Potrony, Miriam (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Bague, Jaume (Hospital Clínic i Provincial de Barcelona)
Cutler, David J. (Emory University School of Medicine)
Álvarez-Mora, María Isabel (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Torres, Teresa (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Barcos, Tamara (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Puig-Butille, Joan Anton (Hospital Clínic i Provincial de Barcelona)
Rubio, Marta (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Madrigal, Irene (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Puig, Susana (Hospital Clínic i Provincial de Barcelona)
Allen, Emily G. (Emory University School of Medicine (Estats Units d'Amèrica))
Rodriguez-Revenga, Laia (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	Fragile X-associated tremor/ataxia syndrome (FXTAS, OMIM# 300623) is a late-onset neurodegenerative disorder with reduced penetrance that appears in adult FMR1 premutation carriers (55-200 CGGs). Clinical symptoms in FXTAS patients usually begin with an action tremor. After that, different findings including ataxia, and more variably, loss of sensation in the distal lower extremities and autonomic dysfunction, may occur, and gradually progress. Cognitive deficits are also observed, and include memory problems and executive function deficits, with a gradual progression to dementia in some individuals. Aquaporin 4 (AQP4) is a commonly distributed water channel in astrocytes of the central nervous system. Changes in AQP4 activity and expression have been implicated in several central nervous system disorders. Previous studies have suggested the associations of AQP4 single nucleotide polymorphisms (SNPs) with brain-water homeostasis, and neurodegeneration disease. To date, this association has not been studied in FXTAS. To investigate the association of AQP4 SNPs with the risk of presenting FXTAS, a total of seven common AQP4 SNPs were selected and genotyped in 95 FMR1 premutation carriers with FXTAS and in 65 FMR1 premutation carriers without FXTAS. The frequency of AQP4 -haplotype was compared between groups, denoting 26 heterozygous individuals and 5 homozygotes as carriers of the minor allele in the FXTAS group and 25 heterozygous and 2 homozygotes in the no-FXTAS group. Statistical analyses showed no significant associations between AQP4 SNPs/haplotypes and development of FXTAS. Although AQP4 has been implicated in a wide range of brain disorders, its involvement in FXTAS remains unclear. The identification of novel genetic markers predisposing to FXTAS or modulating disease progression is critical for future research involving predictors and treatments.
Grants:	Instituto de Salud Carlos III PI17/01067 Instituto de Salud Carlos III PI21/01085 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1134
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	FXTAS ; AQP4 ; FMR1 premutation ; Genetic variation ; Glymphatic system
Published in:	Frontiers in aging neuroscience, Vol. 14 (january 2023) , ISSN 1663-4365

DOI: 10.3389/fnagi.2022.1073258
PMID: 36688175

7 p, 312.9 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles