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
Radiology Department, Hospital Universitari Mútua de Terrassa, Terrassa, Barcelona, Spain.
Institute for Research and Innovation Parc Taulí (I3PT), Sabadell, Spain.
Front Aging Neurosci. 2023 Jan 6;14:1073258. doi: 10.3389/fnagi.2022.1073258. eCollection 2022.
Fragile X-associated tremor/ataxia syndrome (FXTAS, OMIM# 300623) is a late-onset neurodegenerative disorder with reduced penetrance that appears in adult 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 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 SNPs with the risk of presenting FXTAS, a total of seven common SNPs were selected and genotyped in 95 premutation carriers with FXTAS and in 65 premutation carriers without FXTAS.
The frequency of -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 SNPs/haplotypes and development of FXTAS.
Although 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.
脆性X相关震颤/共济失调综合征（FXTAS，OMIM# 300623）是一种迟发性神经退行性疾病，外显率降低，出现在成年前突变携带者（55 - 200个CGG）中。FXTAS患者的临床症状通常始于动作性震颤。此后，可能会出现包括共济失调等不同表现，以及更具变异性的下肢远端感觉丧失和自主神经功能障碍，并逐渐进展。还观察到认知缺陷，包括记忆问题和执行功能缺陷，在一些个体中会逐渐发展为痴呆。水通道蛋白4（AQP4）是中枢神经系统星形胶质细胞中普遍分布的水通道。AQP4活性和表达的变化与几种中枢神经系统疾病有关。先前的研究表明单核苷酸多态性（SNP）与脑水稳态和神经退行性疾病有关。迄今为止，尚未在FXTAS中研究这种关联。
为了研究SNP与患FXTAS风险的关联，总共选择了7个常见SNP，并在95名患有FXTAS的前突变携带者和65名未患FXTAS的前突变携带者中进行基因分型。
比较了两组之间单倍型的频率，在FXTAS组中表示26名杂合子个体和5名纯合子为次要等位基因的携带者，在无FXTAS组中为25名杂合子和2名纯合子。统计分析表明SNP/单倍型与FXTAS的发生之间无显著关联。
尽管已涉及广泛的脑部疾病，但其在FXTAS中的作用仍不清楚。确定导致FXTAS或调节疾病进展的新遗传标记对于未来涉及预测因子和治疗的研究至关重要。
