AbstractHereditary ataxias are classified by inheritance patterns into autosomal dominant, autosomal recessive, X-linked, and mitochondrial modes of inheritance. A large group of adult hereditary ataxias have autosomal dominant inheritance, and autosomal recessive cerebellar ataxias (ARCAs) are rare, with greater diversity in phenotypic and genotypic features.

摘要遗传性共济失调按遗传模式分为常染色体显性遗传，常染色体隐性遗传，X连锁遗传和线粒体遗传模式。大量成人遗传性共济失调具有常染色体显性遗传，常染色体隐性小脑共济失调（ARCA）很少见，在表型和基因型特征上具有更大的多样性。

Therefore, comprehensive genetic testing is useful for identifying the genes responsible for ARCAs. We identified two novel pathogenic variants of the SQSTM1 and SYNE1 genes via whole-exome sequencing in patients with ARCAs..

因此，全面的基因检测可用于鉴定导致ARCA的基因。。。

Hereditary ataxias are classified into autosomal dominant, autosomal recessive, X-linked, and maternal inheritance types on the basis of their type of inheritance1. The diagnosis of hereditary ataxia can be established on the basis of typical neurological findings, a positive family history, and the exclusion of nongenetic ataxias1.

遗传性共济失调根据其遗传类型分为常染色体显性遗传，常染色体隐性遗传，X连锁遗传和母体遗传类型1。遗传性共济失调的诊断可以基于典型的神经学发现，阳性家族史和排除非遗传性共济失调1。

Autosomal recessive cerebellar ataxias (ARCAs) are complex neurodegenerative disorders with highly diverse phenotypes and genotypes2. ARCAs are considered to be early-onset3, unlike the autosomal dominant types, among which the age of onset overlaps1. Various genes have been reported to be responsible for different subtypes of ARCAs, with Friedreich’s ataxia (FRDA gene) and ataxia telangiectasia (ATM gene) being the most common4.

常染色体隐性小脑共济失调（ARCA）是一种复杂的神经退行性疾病，具有高度多样的表型和基因型2。与常染色体显性遗传类型不同，ARCA被认为是早期发作3，其中发病年龄重叠1。据报道，各种基因与ARCA的不同亚型有关，其中弗里德里希的共济失调（FRDA基因）和共济失调毛细血管扩张（ATM基因）是最常见的4。

Although most ARCAs can be distinguished by unique clinical features, definitive diagnosis is challenging because of overlapping phenotypes5. Therefore, it is necessary to use genetic diagnostic methods to identify the different genes responsible for various ARCAs. Over 90 genes have been reported to be associated with ARCAs6.Compared with traditional techniques, next-generation DNA sequencing (NGS) techniques are very powerful, affordable, and fast diagnostic tools for determining the genetic causes of neurological disorders such as ataxia7.

。因此，有必要使用遗传诊断方法来鉴定导致各种ARCA的不同基因。据报道，有90多个基因与ARCAs6相关。与传统技术相比，下一代DNA测序（NGS）技术是非常强大，负担得起且快速的诊断工具，可用于确定神经系统疾病（如共济失调）的遗传原因7。

Recognizing gene defects is a major step in detecting different molecular pathways and is an important prerequisite for the development of effective targeted molecular therapies8. Therefore, this study aimed to identify the genes and mutations associated with autosomal recessive ataxia in two families with consanguineous marriages in Iran.

识别基因缺陷是检测不同分子途径的重要步骤，也是开发有效靶向分子疗法的重要先决条件8。因此，这项研究旨在确定伊朗两个近亲结婚家庭中与常染色体隐性共济失调相关的基因和突变。

In this study, owing to the diverse phenotypic and genotypic features of patients with ARCAs, whole-exome sequencing (WES, an NGS-based test.

在这项研究中，由于ARCAs患者的表型和基因型特征不同，全外显子组测序（WES，一种基于NGS的测试。

HGV database

HGV数据库

The relevant data from this Data Report are hosted at the Human Genome Variation Database at https://doi.org/10.6084/m9.figshare.hgv.3433; https://doi.org/10.6084/m9.figshare.hgv.3436.

该数据报告的相关数据位于人类基因组变异数据库https://doi.org/10.6084/m9.figshare.hgv.3433；https://doi.org/10.6084/m9.figshare.hgv.3436.

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Download referencesAuthor informationAuthors and AffiliationsDepartment of Genetics and Pathology, Ardabil University of Medical Sciences, Ardabil, IranDiana Mokhtari, Mohammad Jahanpanah, Hamed Azari, Sara Arish & Behzad DavarniaDepartment of Animal Biology, Faculty of Natural Science, University of Tabriz, Tabriz, IranNasim JabbariTabriz University of Medical Sciences, Tabriz, IranSana DavarniaDepartment of Biology, Ardabil Branch, Islamic Azad University, Ardabil, IranHaleh MokaberDepartment of Pediatrics, Bo-Ali Children’s Hospital of Ardabil University of Medical Sciences, Ardabil, IranRasol MolatefiCancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, IranRasol MolatefiDepartment of Neurology, Ardabil University of Medical Sciences, Ardabil, IranVahid AbbasiAuthorsDiana MokhtariView author publicationsYou can also search for this author in.

下载参考文献作者信息作者和所属机构阿达比勒医科大学遗传与病理学系，阿达比勒，伊兰迪亚纳·莫赫塔里，穆罕默德·贾汉帕纳，哈米德·阿扎里，萨拉·阿里什和贝扎德·达瓦尼亚动物生物学系，大不里士大学自然科学学院，大不里士，伊兰纳西姆·贾巴里塔布里斯医科大学，大不里士阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达比医科大学，阿达。

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PubMed Google ScholarContributionsB.D. conceived and supervised the study and revised the manuscript. D.M. and M.J. contributed to the laboratory work. D.M., M.J., N.J., H.A., S.D., H.M. and S.A. prepared the manuscript, images, and table. V.A. and R.M. were in charge of the patients’ clinical management and revised the manuscript.Corresponding authorCorrespondence to.

PubMed谷歌学术贡献b。D、 构思并监督了这项研究，并修改了手稿。D、 。五、 A.和R.M.负责患者的临床管理并修订了手稿。对应作者对应。

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Reprints and permissionsAbout this articleCite this articleMokhtari, D., Jahanpanah, M., Jabbari, N. et al. Genetic investigation of patients with autosomal recessive ataxia and identification of two novel variants in the SQSTM1 and SYNE1 genes.

转载和许可本文引用本文Mokhtari，D.，Jahanpanah，M.，Jabbari，N。等人。常染色体隐性共济失调患者的遗传研究以及SQSTM1和SYNE1基因中两个新变异的鉴定。

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