巴西一大群成年起病的未确诊小脑性共济失调患者中GAA相关性共济失调的发生率
Frequency of GAA- Ataxia in a Large Cohort of Brazilian Patients With Unsolved Adult-Onset Cerebellar Ataxia.
作者信息
Novis Luiz Eduardo, Frezatti Rodrigo S, Pellerin David, Tomaselli Pedro J, Alavi Shahryar, Della Coleta Marcus Vinícius, Spitz Mariana, Dicaire Marie-Josée, Iruzubieta Pablo, Pedroso José Luiz, Barsottini Orlando, Cortese Andrea, Danzi Matt C, França Marcondes C, Brais Bernard, Zuchner Stephan, Houlden Henry, Raskin Salmo, Marques Wilson, Teive Helio A
机构信息
From the Pós-graduação Em Medicina Interna e Ciências da Saúde (L.E.N., H.A.T.), Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil; Department of Neuromuscular Diseases (L.E.N., D.P., S.A., P.I., A.C., H.H.), UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurology (R.S.F., P.J.T., W.M.), School of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil; Departments of Neurology and Neurosurgery (D.P., M.-J.D., B.B.), Montreal Neurological Hospital and Institute, McGill University, Canada; Departamento de Neurologia (M.V.D.C.), Universidade do Estado do Amazonas, Manaus; Departamento de Especialidades Médicas (M.S.), Serviço de Neurologia, Universidade Estadual do Rio de Janeiro, Brazil; Department of Neurology (P.I.), Donostia University Hospital; Neuroscience Area (P.I.), Biodonostia Health Research Institute, San Sebastian; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) (P.I.), Spain; Department of Neurology (J.L.P., O.B.), Ataxia Unit, Universidade Federal de São Paulo, SP, Brazil; Department of Brain and Behavioral Sciences (A.C.), University of Pavia, Italy; Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics (M.C.D., S.Z.), University of Miami Miller School of Medicine; Department of Neurology (M.C.F.), School of Medical Sciences-University of Campinas (UNICAMP), São Paulo, Brazil; Department of Human Genetics (B.B.), McGill University, Montreal, Canada; and Laboratório Genetika (S.R.), Curitiba, PR, Brazil.
出版信息
Neurol Genet. 2023 Aug 28;9(5):e200094. doi: 10.1212/NXG.0000000000200094. eCollection 2023 Oct.
OBJECTIVES
Intronic GAA repeat expansions have recently been found to be a common cause of hereditary ataxia (GAA- 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- 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 repeat locus. Patients were recruited across 4 different regions of Brazil.
RESULTS
Of the 93 index patients, 8 (9%) carried an (GAA) 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) expansion developed ataxia at age 28 years, confirming that GAA- 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- ataxia is a common cause of adult-onset ataxia in the Brazilian population, although larger studies are needed to fully define its epidemiology.
目的
内含子GAA重复序列扩增最近被发现是遗传性共济失调（GAA型共济失调；SCA27B）的常见病因。这种新报道疾病的全球流行病学和区域患病率仍有待确定。在本研究中，我们调查了一大群成年起病、病因未明的巴西共济失调患者中GAA型共济失调的发生频率。
方法
我们招募了93例尽管经过广泛基因检测但病因仍未明确的成年起病共济失调患者，并对其重复序列位点进行基因分型。患者来自巴西4个不同地区。
结果
93例索引患者中，8例（9%）存在（GAA）扩增。在1名患病亲属中也发现了这种扩增。7例患者为欧洲血统，1例为非洲血统，1例为美国混血血统。1例携带（GAA）扩增的患者在28岁时出现共济失调，证实GAA型共济失调可在30岁之前发病。1例患者表现为发作性症状，而所有患者均无下跳性眼球震颤。8例患者中有7例（87%）脑部MRI显示小脑萎缩。
讨论
我们的结果表明，GAA型共济失调是巴西成年起病共济失调的常见病因，尽管需要更大规模的研究来全面界定其流行病学特征。
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