由senataxin基因的大规模缺失引起的共济失调和动眼肌失用症。

IF 1.9 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Joanna M Rusecka, Biruta Kierdaszuk, Iwona Stępniak, Małgorzata Rydzanicz, Piotr Stawiński, Tomasz Gambin, Damian Loska, Magdalena M Kacprzak, Magdalena Kaliszewska, Dorota Piekutowska-Abramczuk, Anna M Kamińska, Ewa Pronicka, Ewa Bartnik, Anna Kostera-Pruszczyk, Rafał Płoski, Agnieszka Sobczyńska-Tomaszewska, Katarzyna Tońska
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引用次数: 0

摘要

Senataxin是一种RNA/DNA解旋酶,是提供基因组稳定性的关键蛋白,也是最具特征的r环结合因子之一,在转录和DNA修复过程中发挥重要作用。致病性SETX基因变异导致常染色体隐性脊髓小脑共济失调伴轴突神经病变(AOA2, MIM #606002)和常染色体显性幼年肌萎缩侧索硬化症(ALS4, MIM #602433),这是一种罕见的神经退行性疾病,其特征是幼年发病的进行性小脑共济失调、轴突感觉运动周围神经病变、上下运动神经元合并症状和血清甲胎儿蛋白(AFP, AOA2特异性)升高。我们报告了两例成人患者,他们在生命的第二/第三个十年开始出现小脑综合征,扫描语言和运动不耐受,随后出现肌肉无力和步态协调受损。采用全外显子组测序(WES)分析单核苷酸和拷贝数变异。9号染色体(chr9:132,295,852-132,311,876)上约16 kb的基因组区域覆盖率下降,表明SETX基因缺失了5个外显子(外显子11-15,NM_015046.7)。这种纯合子SETX (9q34.13)的缺失导致帧移位,从而导致蛋白解旋酶结构域的截断。已知SETX基因的功能缺失变异具有致病性。对波兰人口NGS数据的统计分析发现了一些杂合携带者,表明其具有区域特异性起源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ataxia and oculomotor apraxia caused by a large-scale deletion in the senataxin gene.

Senataxin, an RNA/DNA helicase, is a key protein providing genome stability and one of the best characterized R-loop-binding factors playing an important role in transcription and DNA repair processes. Pathogenic SETX gene variants cause autosomal recessive spinocerebellar ataxia with axonal neuropathy (AOA2, MIM #606002) and autosomal dominant juvenile amyotrophic lateral sclerosis (ALS4, MIM #602433), rare neurodegenerative disorders characterized by juvenile onset of progressive cerebellar ataxia, axonal sensorimotor peripheral neuropathy, combined upper and lower motor neuron symptoms, and increased serum alpha-fetoprotein (AFP; specific for AOA2). We report two cases of adult patients presenting with cerebellar syndrome, scanned speech, and exercise intolerance which started in the second/third decade of life and were followed by muscle weakness and impaired gait coordination. Whole exome sequencing (WES) was performed to analyze single nucleotide and copy number variants. A decreased coverage of a genomic region of around 16 kb on chromosome 9 (chr9:132,295,852-132,311,876), suggesting a deletion encompassing 5 exons of the SETX gene (exons 11-15, NM_015046.7) was observed. This homozygous SETX (9q34.13) deletion leads to a frame shift and consequently truncation of the helicase domain in the protein. Loss-of-function variants in the SETX gene are known to be pathogenic. Statistical analysis of NGS data from the Polish population identified a few heterozygous carriers, suggesting its region-specific origin.

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来源期刊
Journal of Applied Genetics
Journal of Applied Genetics 生物-生物工程与应用微生物
CiteScore
4.30
自引率
4.20%
发文量
62
审稿时长
6-12 weeks
期刊介绍: The Journal of Applied Genetics is an international journal on genetics and genomics. It publishes peer-reviewed original papers, short communications (including case reports) and review articles focused on the research of applicative aspects of plant, human, animal and microbial genetics and genomics.
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