Abstract：
BACKGROUND: Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10).
METHODS: Following the MDSGene protocol, we systematically investigated genotype-phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients.
RESULTS: Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis.
CONCLUSIONS: The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
METHODS: Following the MDSGene protocol, we systematically investigated genotype-phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients.
RESULTS: Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis.
CONCLUSIONS: The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
摘要：
背景：ANO10基因的双等位基因致病变异导致常染色体隐性遗传进行性共济失调（ATX-ANO10）。
方法：遵循MDSGene协议，我们根据82例已发表的患者和12例新发现的患者的临床和遗传数据,系统研究了ATX-ANO10的基因型-表型关系.
结果：大多数患者（>80％）具有功能丧失（LOF）变异。最常见的变体是c.1150_1151del，在所有29名罗马血统患者中发现，与其他LOF变异纯合的患者相比，发病时的平均年龄早14岁。我们确定了ATX-ANO10的先前未描述的临床特征(例如，面部肌肉受累和斜视）提示脑干病理受累，我们提出了一种诊断算法，可以帮助临床ATX-ANO10诊断。
结论：c.1150_1151del患者的早期疾病发作可能表明Romani人群中存在遗传/环境疾病改变因素。我们的发现将为患者提供咨询，并可能提高我们对疾病机制的理解。©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。
方法：遵循MDSGene协议，我们根据82例已发表的患者和12例新发现的患者的临床和遗传数据,系统研究了ATX-ANO10的基因型-表型关系.
结果：大多数患者（>80％）具有功能丧失（LOF）变异。最常见的变体是c.1150_1151del，在所有29名罗马血统患者中发现，与其他LOF变异纯合的患者相比，发病时的平均年龄早14岁。我们确定了ATX-ANO10的先前未描述的临床特征(例如，面部肌肉受累和斜视）提示脑干病理受累，我们提出了一种诊断算法，可以帮助临床ATX-ANO10诊断。
结论：c.1150_1151del患者的早期疾病发作可能表明Romani人群中存在遗传/环境疾病改变因素。我们的发现将为患者提供咨询，并可能提高我们对疾病机制的理解。©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。
