Sena Lucas Schenatto, Medeiros Leonardo Simão, Jardim Laura Bannach
Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Centros de Pesquisa Clínica E Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Cerebellum. 2025 Jun 4;24(4):108. doi: 10.1007/s12311-025-01854-7.
Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a CAG expansion (CAGexp) disease whose genetic characteristics in South America (SA) are not well known. Our aim was to perform a systematic review and meta-analysis on the subject. Number of SA cases, ages at onset (AO), normal CAG repeats (CAGnormal) and CAGexp, and haplotypes, were searched in Pubmed, Embase, Lilacs, SciELO, ProQuest™ Dissertations & Theses Citation Index, BDTD and La Referencia by a PROSPERO registered protocol. Quantitative data were meta analysed. 26 non-replicated papers and dissertations out of 713 publications were included. 2,111 SCA3/MJD patients were reported, 16 living in Argentina, 10 in Chile, 41 in Venezuela, 18 in Peru, and 2,026 in Brazil between 2011 and 2024. Four individual-participant data (IPD) were obtained. The mean (95% CI; sample size) of CAGnormal, CAGexp and AO were 21.90 (21.53-22.27; 802) and 74.65 (74.43-74.87; 1,100) repeats, and 34.90 (34.25-35.31; 1,102) years. CAGexp explained 62% of the AO variability in IPD (789). The CAGexp effects over AO varied according to geographical origin, impacting in the models to predict AO. It was similar in three Brazilian cohorts, while among Peruvians the AO seemed to be earlier than expected by their CAGexp legths. Three studies found the rs1048755-rs12895357-rs7158733 haplotypes ACA, CCG and AGA in Brazilian patients. In conclusion, current evidence supports the relationship between SCA3/MJD and Portuguese-Azoreans, while the different CAGexp effects on AO across SA populations need to be studied to determine the underlying modifying factors.
3型脊髓小脑共济失调/马查多-约瑟夫病（SCA3/MJD）是一种CAG重复序列扩增（CAGexp）疾病，其在南美洲（SA）的遗传特征尚不清楚。我们的目的是对该主题进行系统综述和荟萃分析。通过PROSPERO注册协议在PubMed、Embase、Lilacs、SciELO、ProQuest™ 学位论文引文索引、BDTD和La Referencia中搜索SA病例数、发病年龄（AO）、正常CAG重复序列（CAGnormal）和CAGexp以及单倍型。对定量数据进行荟萃分析。在713篇出版物中纳入了26篇未重复的论文和学位论文。报告了2111例SCA3/MJD患者，2011年至2024年间，16例生活在阿根廷，10例在智利，41例在委内瑞拉，18例在秘鲁，2026例在巴西。获得了4份个体参与者数据（IPD）。CAGnormal、CAGexp和AO的平均值（95%CI；样本量）分别为21.90（21.53 - 22.27；802）和74.65（74.43 - 74.87；1100）次重复，以及34.90（34.25 - 35.31；1102）岁。CAGexp解释了IPD中AO变异性的62%（789）。CAGexp对AO的影响因地理来源而异，影响预测AO的模型。在三个巴西队列中情况相似，而在秘鲁人中，AO似乎比根据其CAGexp长度预期的要早。三项研究在巴西患者中发现了rs1048755 - rs12895357 - rs7158733单倍型ACA、CCG和AGA。总之，目前的证据支持SCA3/MJD与葡萄牙亚速尔人之间的关系，而SA人群中CAGexp对AO的不同影响需要进一步研究以确定潜在的修饰因素。
