中断的ATXN10重复序列扩增对10型脊髓小脑共济失调临床症状的影响

The impact of interrupted ATXN10 expansions on clinical findings of spinocerebellar ataxia type 10.

作者信息

Hasan Ali, Furtado Gabriel Vasata, Miglorini Elaine, Mergener Rafaella, Massuyama Breno, Barsottini Orlando, Pedroso José Luiz, Teive Helio G, Saraiva-Pereira Maria Luiza, Ashizawa Tetsuo, Jardim Laura Bannach

机构信息

Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Centros de Pesquisa Clínica e Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

出版信息

J Neurol. 2025 Mar 11;272(4):261. doi: 10.1007/s00415-025-13003-5.

DOI:10.1007/s00415-025-13003-5

PMID:40067487

Abstract

BACKGROUND

Spinocerebellar ataxia type 10 (SCA10), due to an ATTCT repeat expansion in ATXN10, has variable expressivity and the role of presence (ATTCTint +) and absence (ATTCTint-) of interruptions in the repeat is not clear. We aimed to describe the relations between ATTCTint + and age at onset, seizures, and neurologic severity in ataxic and non-ataxic carriers from Brazil.

METHODS

Family, age at onset (AO), and seizures data plus DNA were obtained from symptomatic carriers already diagnosed in Porto Alegre, Curitiba, and São Paulo, Brazil. Patients and their relatives were invited to be evaluated through Scale of Assessment and Rating of Ataxia (SARA) and other clinical scales; a SARA > 2.5 classified subjects as ataxic carriers. Repeat-primed PCR (RP-PCR) defined the expansions with (ATTCTint +) or without (ATTCTint-) interruptions. Comparisons were performed for a p level of 0.05.

RESULTS

Among 78 ataxic carriers, earlier AO (p = 0.039) and higher occurrences of epilepsy (p < 0.0001) were seen in subjects with ATTCTint + than in those with ATTCTint-. Clinical scales were worse in 34 ataxics than in 7 non-ataxics and 10 related controls (p = 0.006) and did not discriminate non-ataxics from controls. The 11 ataxic ATTCTint + carriers had higher SARA scores per year of disease duration than the 23 ATTCTint- carriers (r = 0.879, beta = 0.45, p = 0.0001).

DISCUSSION

ATTCTint + carriers had worse clinical findings than ATTCTint- carriers: earlier AO, more seizures, and worse ataxia scores. Interruptions in the expanded repeat have a real impact in SCA10 phenotype.

摘要

背景

10型脊髓小脑共济失调（SCA10）由ATXN10基因中的ATTCT重复序列扩增引起，具有可变表达性，重复序列中存在（ATTCTint +）和不存在（ATTCTint -）中断的作用尚不清楚。我们旨在描述巴西共济失调和非共济失调携带者中ATTCTint +与发病年龄、癫痫发作及神经严重程度之间的关系。

方法

从巴西阿雷格里港、库里蒂巴和圣保罗已确诊的有症状携带者处获取家族史、发病年龄（AO）、癫痫发作数据及DNA。邀请患者及其亲属通过共济失调评估和评分量表（SARA）及其他临床量表进行评估；SARA评分>2.5将受试者分类为共济失调携带者。重复引物PCR（RP-PCR）确定有（ATTCTint +）或无（ATTCTint -）中断的扩增情况。比较的p值设定为0.05。

结果

在78名共济失调携带者中，与ATTCTint -携带者相比，ATTCTint +携带者的发病年龄更早（p = 0.039），癫痫发作发生率更高（p < 0.0001）。34名共济失调患者的临床量表评分比7名非共济失调患者和10名相关对照更差（p = 0.006），且无法区分非共济失调患者与对照。11名携带ATTCTint +的共济失调携带者每患病一年的SARA评分高于23名携带ATTCTint -的携带者（r = 0.879，β = 0.45，p = 0.0001）。