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
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.
['Zhao|Hua|H|', 'Yang|Lu|L|', 'Dong|Yi|Y|', 'Wu|Zhi-Ying|ZY|0000-0003-2106-572X']
D000328:Adult D000067699:Ataxin-3 D000073537:Biological Variation, Population D018899:CpG Islands D019175:DNA Methylation D005260:Female D006801:Humans D017827:Machado-Joseph Disease D012097:Repressor Proteins D019680:Trinucleotide Repeat Expansion D014430:Twins, Monozygotic
phenotypic variance monozygotic twin spinocerebellar ataxia type 3 DNA methylation