Abstract：
BACKGROUND: FRMD5 variants were recently identified in patients with developmental delay, ataxia, and eye movement abnormalities.
OBJECTIVE: We describe 2 patients presenting with childhood-onset ataxia, nystagmus, and seizures carrying pathogenic de novo FRMD5 variants. Weighted gene co-expression network analysis (WGCNA) was performed to gain insights into the function of FRMD5 in the brain.
METHODS: Trio-based whole-exome sequencing was performed in both patients, and CoExp web tool was used to conduct WGCNA.
RESULTS: Both patients presented with developmental delay, childhood-onset ataxia, nystagmus, and seizures. Previously unreported findings were diffuse choreoathetosis and dystonia of the hands (patient 1) and areas of abnormal magnetic resonance imaging signal in the white matter (patient 2). WGCNA showed that FRMD5 belongs to gene networks involved in neurodevelopment and oligodendrocyte function.
CONCLUSIONS: We expanded the phenotype of FRMD5-related disease and shed light on its role in brain function and development. We recommend including FRMD5 in the genetic workup of childhood-onset ataxia and nystagmus. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
OBJECTIVE: We describe 2 patients presenting with childhood-onset ataxia, nystagmus, and seizures carrying pathogenic de novo FRMD5 variants. Weighted gene co-expression network analysis (WGCNA) was performed to gain insights into the function of FRMD5 in the brain.
METHODS: Trio-based whole-exome sequencing was performed in both patients, and CoExp web tool was used to conduct WGCNA.
RESULTS: Both patients presented with developmental delay, childhood-onset ataxia, nystagmus, and seizures. Previously unreported findings were diffuse choreoathetosis and dystonia of the hands (patient 1) and areas of abnormal magnetic resonance imaging signal in the white matter (patient 2). WGCNA showed that FRMD5 belongs to gene networks involved in neurodevelopment and oligodendrocyte function.
CONCLUSIONS: We expanded the phenotype of FRMD5-related disease and shed light on its role in brain function and development. We recommend including FRMD5 in the genetic workup of childhood-onset ataxia and nystagmus. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
摘要：
背景：最近在发育迟缓患者中发现了FRMD5变异，共济失调,和眼球运动异常。
目的：我们描述了2例儿童共济失调患者，眼球震颤,以及携带致病性从头FRMD5变异体的癫痫发作。进行加权基因共表达网络分析(WGCNA)以获得对大脑中FRMD5功能的了解。
方法：对两名患者进行了基于Trio的全外显子组测序，使用CoExp网络工具进行WGCNA。
结果：两名患者均出现发育迟缓，儿童期共济失调,眼球震颤,和癫痫发作。以前未报告的发现是弥漫性舞蹈性关节炎和手部肌张力障碍（患者1）以及白质中异常磁共振成像信号的区域（患者2）。WGCNA显示FRMD5属于参与神经发育和少突胶质细胞功能的基因网络。
结论：我们扩展了FRMD5相关疾病的表型，并阐明了其在脑功能和发育中的作用。我们建议在儿童共济失调和眼球震颤的遗传检查中包括FRMD5。©2024作者由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
目的：我们描述了2例儿童共济失调患者，眼球震颤,以及携带致病性从头FRMD5变异体的癫痫发作。进行加权基因共表达网络分析(WGCNA)以获得对大脑中FRMD5功能的了解。
方法：对两名患者进行了基于Trio的全外显子组测序，使用CoExp网络工具进行WGCNA。
结果：两名患者均出现发育迟缓，儿童期共济失调,眼球震颤,和癫痫发作。以前未报告的发现是弥漫性舞蹈性关节炎和手部肌张力障碍（患者1）以及白质中异常磁共振成像信号的区域（患者2）。WGCNA显示FRMD5属于参与神经发育和少突胶质细胞功能的基因网络。
结论：我们扩展了FRMD5相关疾病的表型，并阐明了其在脑功能和发育中的作用。我们建议在儿童共济失调和眼球震颤的遗传检查中包括FRMD5。©2024作者由WileyPeriodicalsLLC代表国际帕金森症和运动障碍协会出版的运动障碍。
