SCA3 同卵双胞胎的表型变异。
Phenotypic variance in monozygotic twins with SCA3.
机构信息
Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.
出版信息
Mol Genet Genomic Med. 2020 Oct;8(10):e1438. doi: 10.1002/mgg3.1438. Epub 2020 Jul 29.
BACKGROUND
Spinocerebellar ataxia type 3 (SCA3) is a hereditary neurodegenerative disorder with high clinical heterogeneity. Twin study is valuable to estimate the contributions of gene and/or environment to phenotypic variance. However, SCA3 twins were extremely sparse and rarely reported.
METHODS
A pair of monozygotic twins with SCA3 was assessed using well-acknowledged scales. Genetic modifiers and methylation levels were determined by Sanger sequencing and pyrosequencing.
RESULTS
Sharing identical CAG repeat lengths, the twins presented with similar symptoms, whereas, the younger sister had an earlier age at onset of two years. The occurrence time and severity of constipation, blepharospasm and fasciculation were markedly different between the twins. Notable methylation level differences of several CpG sites existed between the twins.
CONCLUSIONS
It is the first time to report SCA3 monozygotic twin worldwide. The role of epigenetic factors in the phenotype variance deserved more attention. The DNA methylation may influence the phenotypic variance by altering the occurrence time and severity of symptoms, indicating its potential in alleviating the disease.
背景
脊髓小脑性共济失调 3 型（SCA3）是一种具有高度临床异质性的遗传性神经退行性疾病。双胞胎研究对于评估基因和/或环境对表型变异的贡献很有价值。然而，SCA3 双胞胎极其罕见，鲜有报道。
方法
使用公认的量表评估一对 SCA3 同卵双胞胎。通过 Sanger 测序和焦磷酸测序确定遗传修饰因子和甲基化水平。
结果
双胞胎共享相同的 CAG 重复长度，表现出相似的症状，而妹妹的发病年龄早了两年。便秘、眼睑痉挛和肌束震颤在双胞胎之间的发生时间和严重程度有明显差异。双胞胎之间存在几个 CpG 位点的显著甲基化水平差异。
结论
这是全球首次报道 SCA3 同卵双胞胎。表观遗传因素在表型变异中的作用值得更多关注。DNA 甲基化可能通过改变症状的发生时间和严重程度来影响表型变异，表明其在缓解疾病方面具有潜力。
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