Factors Associated with Intergenerational Instability of ATXN3 CAG Repeat and Genetic Anticipation in Chinese Patients w
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SHORT REPORTS
Factors Associated with Intergenerational Instability of ATXN3 CAG Repeat and Genetic Anticipation in Chinese Patients with Spinocerebellar Ataxia Type 3 Yi-Chu Du 1 & Yin Ma 1 & Ya-Ru Shao 1 & Shi-Rui Gan 2 & Yi Dong 1,3 & Zhi-Ying Wu 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Spinocerebellar ataxia type 3 (SCA3) is caused by unstable expanded CAG repeats (expCAGs) in ATXN3. Factors associated with intergenerational instability (delta-expCAG) and genetic anticipation in SCA3 have never been reported in Chinese mainland. Here, we demonstrated that unstable transmissions occurred more often in sons than in daughters (91% vs 72%, Fisher’s exact test, p = 0.012). The extended delta-expCAG of father-son transmissions was greater than that of mother-son transmissions (3.8 ± 2.3 repeats vs 1.6 ± 1.0 repeats, Mann-Whitney U, p = 0.001). Genetic anticipation was frequently observed between generations but not affected by the delta-expCAG. Keywords Spinocerebellar ataxia type 3 . Intergenerational transmission . Genetic anticipation . Chinese
Introduction Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of spinocerebellar ataxias (SCAs) in the Chinese population. It is an autosomal dominant neurodegenerative disease caused by an unstable expansion of CAG repeats in ATXN3 [1]. The age at onset (AAO) of SCA3 is mostly modified by the size of the expanded CAG repeats (expCAGs). During intergenerational transmission, the expCAG instability and genetic anticipation are the features in polyglutamine (polyQ) diseases such as Huntington’s disease (HD) and SCAs [2–4]. Moreover, this transmitted instability (i.e., delta-expCAG) is thought to explain the phenotype, such as Yi-Chu Du and Yin Ma contributed equally to this work.
genetic anticipation [5]. Revealing the factors associated with CAG instability and genetic anticipation would be helpful in clinical practice in SCA3 and helpful to unveil underlying mechanism in polyQ diseases. Indeed, factors affecting the transmitted instability in polyQ disease remain inconsistent. More factors associated with the transmitted instability are still under research [6, 7, 8]. As genotype in SCA3 varied in different populations, investigations of affecting factors in different populations are of great vital. The associated factors of transmitted instability have been reported in Japanese, Brazilian, and Portuguese [5, 7, 9], but few have been documented in Chinese except Chinese people in Taiwan [ 10, 11]. Here, we aim to investigate the factors associated with intergenerational instability of CAG repeats and genetic anticipation in mainland Chinese SCA3 patients.
* Zhi-Ying Wu [email protected] 1
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 310009, China
2
Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fu
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