Frequency of GAA- <i>FGF14</i> Ataxia in a Large Cohort of Brazilian Patients With Unsolved Adult-Onset Cerebellar Ataxia
Luiz Eduardo Novis, Rodrigo Siqueira Soares Frezatti, David Pellerin, Pedro José Tomaselli, Shahryar Alavi, Marcus Vinícius Della Coleta, Mariana Spitz, Marie‐Josée Dicaire, Pablo Iruzubieta, José Luiz Pedroso, Orlando Graziani Póvoas Barsottini, Andrea Cortese, Matt C. Danzi, Marcondes C. França, Bernard Brais, Stephan Züchner, Henry Houlden, Salmo Raskin, Wilson Marques, Hélio Afonso Ghizoni Teive
Abstract
<h3>Objectives</h3> Intronic <i>FGF14</i> GAA repeat expansions have recently been found to be a common cause of hereditary ataxia (GAA-<i>FGF14</i> 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-<i>FGF14</i> ataxia in a large cohort of Brazilian patients with unsolved adult-onset ataxia. <h3>Methods</h3> We recruited 93 index patients with genetically unsolved adult-onset ataxia despite extensive genetic investigation and genotyped the <i>FGF14</i> repeat locus. Patients were recruited across 4 different regions of Brazil. <h3>Results</h3> Of the 93 index patients, 8 (9%) carried an <i>FGF14</i> (GAA)<sub>≥250</sub> 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)<sub>376</sub> expansion developed ataxia at age 28 years, confirming that GAA-<i>FGF14</i> 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%). <h3>Discussion</h3> Our results suggest that GAA-<i>FGF14</i> ataxia is a common cause of adult-onset ataxia in the Brazilian population, although larger studies are needed to fully define its epidemiology.