Frequency of GAA-FGF14 Ataxia in a Large Cohort of Brazilian Patients With Unsolved Adult-Onset Cerebellar Ataxia.

IF 3 3区医学 Q2 CLINICAL NEUROLOGY Neurology-Genetics Pub Date : 2023-08-28 eCollection Date: 2023-10-01 DOI:10.1212/NXG.0000000000200094

Luiz Eduardo Novis, Rodrigo S Frezatti, David Pellerin, Pedro J Tomaselli, Shahryar Alavi, Marcus Vinícius Della Coleta, Mariana Spitz, Marie-Josée Dicaire, Pablo Iruzubieta, José Luiz Pedroso, Orlando Barsottini, Andrea Cortese, Matt C Danzi, Marcondes C França, Bernard Brais, Stephan Zuchner, Henry Houlden, Salmo Raskin, Wilson Marques, Helio A Teive

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Abstract

Objectives: Intronic FGF14 GAA repeat expansions have recently been found to be a common cause of hereditary ataxia (GAA-FGF14 ataxia; SCA27B). The global epidemiology and regional prevalence of this newly reported disorder remain to be established. In this study, we investigated the frequency of GAA-FGF14 ataxia in a large cohort of Brazilian patients with unsolved adult-onset ataxia.

Methods: We recruited 93 index patients with genetically unsolved adult-onset ataxia despite extensive genetic investigation and genotyped the FGF14 repeat locus. Patients were recruited across 4 different regions of Brazil.

Results: Of the 93 index patients, 8 (9%) carried an FGF14 (GAA)_≥250 expansion. The expansion was also identified in 1 affected relative. Seven patients were of European descent, 1 was of African descent, and 1was of admixed American ancestry. One patient carrying a (GAA)₃₇₆ expansion developed ataxia at age 28 years, confirming that GAA-FGF14 ataxia can occur before the age of 30 years. One patient displayed episodic symptoms, while none had downbeat nystagmus. Cerebellar atrophy was observed on brain MRI in 7 of 8 patients (87%).

Discussion: Our results suggest that GAA-FGF14 ataxia is a common cause of adult-onset ataxia in the Brazilian population, although larger studies are needed to fully define its epidemiology.

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GAA-FGF14共济失调在未解决的成年性小脑性共济失调的巴西大队列患者中的频率

目的：最近发现内含子FGF14-GAA重复扩增是遗传性共济失调的常见原因（GAA-FGF14-ataxia；SCA27B）。这种新报告的疾病的全球流行病学和区域流行率仍有待确定。在这项研究中，我们调查了GAA-FGF14共济失调在未解决的成年发病共济失调的巴西患者中的频率。方法：尽管进行了广泛的基因调查，我们还是招募了93名遗传上未解决的成年发作性共济失调患者，并对FGF14重复基因座进行了基因分型。在巴西的4个不同地区招募了患者。结果：在93名指数患者中，8名（9%）的FGF14（GAA）≥250扩增。在1名受影响的亲属中也发现了扩张。7名患者为欧洲后裔，1名为非洲后裔，1例为美国混血儿。一名携带（GAA）376扩增的患者在28岁时出现共济失调，证实GAA-FGF14共济失调可能发生在30岁之前。一名患者表现出发作性症状，而没有一名患者出现心跳减慢的眼球震颤。8名患者中有7名（87%）在脑MRI上观察到小脑萎缩。讨论：我们的研究结果表明，GAA-FGF14共济失调是巴西人群中成人发作性共济失调的常见原因，尽管需要更大规模的研究来全面确定其流行病学。

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

Neurology-Genetics Medicine-Neurology (clinical)

CiteScore

6.30

自引率

3.20%

发文量

107

审稿时长

15 weeks

期刊介绍： Neurology: Genetics is an online open access journal publishing peer-reviewed reports in the field of neurogenetics. Original articles in all areas of neurogenetics will be published including rare and common genetic variation, genotype-phenotype correlations, outlier phenotypes as a result of mutations in known disease-genes, and genetic variations with a putative link to diseases. This will include studies reporting on genetic disease risk and pharmacogenomics. In addition, Neurology: Genetics will publish results of gene-based clinical trials (viral, ASO, etc.). Genetically engineered model systems are not a primary focus of Neurology: Genetics, but studies using model systems for treatment trials are welcome, including well-powered studies reporting negative results.