The First Case of Autosomal Recessive Cerebellar Ataxia with Prominent Paroxysmal Non-kinesigenic Dyskinesia Caused by a Truncating FGF14 Variant in a Turkish Patient

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2024-12-20 DOI:10.1002/mds.30087

Dilşad Türkdoğan MD, Natalia Smolina PhD, Şeyma Tekgül MSc, Tuğçe Gül PhD, Ahmet Yeşilyurt MD, Henry Houlden MD, PhD, Stephan Zuchner MD, PhD, Bernard Brais MDCM, PhD, David Pellerin MD, Ayşe Nazlı Başak PhD

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引用次数: 0

Abstract

Background

ATX-FGF/SCA27A has been exclusively associated with heterozygous variants in the FGF14 gene, presenting with postural tremor, slowly progressive cerebellar ataxia, and psychiatric and behavioral disturbances.

Objectives

This study describes the first case of ATX-FGF/SCA27A linked to a biallelic frameshift variant in the FGF14 gene.

Methods

Whole-exome sequencing (WES) was conducted using the Illumina NovaSeq 6000 platform, and the identified variant was confirmed using Sanger sequencing.

Results

We report the first case of autosomal recessive FGF14-related cerebellar ataxia caused by a c.75del variant resulting in p.Leu26Serfs*51 truncation of the FGF14 protein. This variant was found in a patient born to consanguineous parents and presented with a complex congenital nonprogressive cerebellar disorder accompanied by neurodevelopmental delay, intellectual disability, and prominent drug-responsive paroxysmal non-kinesigenic dyskinesia. Segregation analysis confirmed that the homozygous variant was inherited from heterozygous parents who developed mild gait ataxia and tremor in their 40s.

Conclusions

Biallelic loss-of-function variants in FGF14 are a rare cause of inherited cerebellar ataxia and expand the current genetic spectrum of ATX-FGF14. © 2024 International Parkinson and Movement Disorder Society.

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一例常染色体隐性小脑共济失调伴突发性非运动性运动障碍，由截断型FGF14变异引起。

背景：ATX-FGF/SCA27A仅与FGF14基因的杂合变异相关，表现为体位性震颤、缓慢进行性小脑共济失调以及精神和行为障碍。目的：本研究描述了首个与FGF14基因双等位移码变异相关的ATX-FGF/SCA27A病例。方法：使用Illumina NovaSeq 6000平台进行全外显子组测序（WES），并使用Sanger测序确认鉴定的变异。结果：我们报告了第一例常染色体隐性FGF14相关小脑性共济失调，由c.75del变异引起的p.Leu26Serfs*51截断FGF14蛋白。该变异在一名近亲父母所生的患者中被发现，该患者表现为复杂的先天性非进行性小脑疾病，伴有神经发育迟缓、智力残疾和突出的药物反应性阵发性非运动障碍。分离分析证实，纯合变异遗传自40多岁时出现轻度步态共济失调和震颤的杂合父母。结论：FGF14的双等位基因功能缺失变异是遗传性小脑性共济失调的罕见原因，并扩大了目前ATX-FGF14的遗传谱。©2024国际帕金森和运动障碍学会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.