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Phenotypic variance in monozygotic twins with SCA3

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...

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Detalles Bibliográficos
Autores principales: Zhao, Hua, Yang, Lu, Dong, Yi, Wu, Zhi‐Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549591/
https://www.ncbi.nlm.nih.gov/pubmed/32729243
http://dx.doi.org/10.1002/mgg3.1438
Descripción
Sumario: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.