AUTHOR=Elias-Mas Andrea , Potrony Miriam , Bague Jaume , Cutler David J. , Alvarez-Mora Maria Isabel , Torres Teresa , Barcos Tamara , Puig-Butille Joan Anton , Rubio Marta , Madrigal Irene , Puig Susana , Allen Emily G. , Rodriguez-Revenga Laia 

TITLE=Evaluation of AQP4 functional variants and its association with fragile X-associated tremor/ataxia syndrome

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.1073258

DOI=10.3389/fnagi.2022.1073258

ISSN=1663-4365

ABSTRACT=<sec><title>Introduction</title><p>Fragile X-associated tremor/ataxia syndrome (FXTAS, OMIM# 300623) is a late-onset neurodegenerative disorder with reduced penetrance that appears in adult <italic>FMR1</italic> 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 <italic>AQP4</italic> single nucleotide polymorphisms (SNPs) with brain-water homeostasis, and neurodegeneration disease. To date, this association has not been studied in FXTAS.</p></sec><sec><title>Methods</title><p>To investigate the association of <italic>AQP4</italic> SNPs with the risk of presenting FXTAS, a total of seven common <italic>AQP4</italic> SNPs were selected and genotyped in 95 <italic>FMR1</italic> premutation carriers with FXTAS and in 65 <italic>FMR1</italic> premutation carriers without FXTAS.</p></sec><sec><title>Results</title><p>The frequency of <italic>AQP4</italic>-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 <italic>AQP4</italic> SNPs/haplotypes and development of FXTAS.</p></sec><sec><title>Discussion</title><p>Although <italic>AQP4</italic> 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.</p></sec>