未经证实: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FMR1前突变携带者(55-200CGG)中。FXTAS患者的临床症状通常始于行动性震颤。之后,不同的发现,包括共济失调,更不同的是,下肢远端感觉丧失和自主神经功能障碍,可能发生,并逐渐进步。还观察到认知缺陷,包括记忆问题和执行功能缺陷,一些人逐渐发展为痴呆症。水通道蛋白4(AQP4)是中枢神经系统星形胶质细胞中一种普遍散布的水通道。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AQP4单核苷酸多态性(SNP)与脑-水稳态的关联,和神经退行性疾病。迄今为止,这种关联尚未在FXTAS中进行研究。
未经证实:为了调查AQP4SNP与FXTAS的风险的关联,在95个有FXTAS的FMR1前突变携带者和65个无FXTAS的FMR1前突变携带者中,共筛选出7个常见AQP4SNP并进行基因分型.
UNASSIGNED:在组间比较AQP4单倍型的频率,在FXTAS组中表示26个杂合个体和5个纯合子为次要等位基因的携带者,在no-FXTAS组中表示25个杂合和2个纯合子。统计分析显示AQP4SNP/单倍型与FXTAS的发展之间没有显着关联。
未经批准:尽管AQP4与广泛的脑部疾病有关,其参与FXTAS仍不清楚。鉴定易患FXTAS或调节疾病进展的新型遗传标记对于涉及预测因子和治疗的未来研究至关重要。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.