ABSTRACT

Introduction

Previously published studies demonstrated that mutations in CWF19L1 cause early-onset autosomal recessive cerebellar ataxia 17. In this article, we report a novel homozygous missense variant in CWF19L1 in two sisters who had late-onset cerebellar ataxia with epilepsy and describe their clinical and neuroradiological findings.

Methods

We included two female patients with typical symptoms of cerebellar ataxia supported by the MRI findings. Whole exome sequencing (WES) data analysis was performed to identify the underlying genetic defect in the proband. Sanger sequencing was used to confirm the variant in other family members.

Results

WES revealed a homozygous missense variant in CWF19-like protein 1; CWF19L1 gene c.395A>G; p.(Asp132Gly) (RefSeq NM_018294.4). This variant has not been described previously in the literature. Mutations in this gene are known to cause an autosomal recessive disorder, spinocerebellar ataxia, autosomal recessive 17 (OMIM #616127).

Conclusion

In conclusion, we report a novel variant in CWF19L1 as a candidate causal variant in two sisters with autosomal recessive cerebellar ataxia. This is the first report coming from Arab countries. Additional reports in patients with a progressive course and adult-onset are needed, but this could be the first report of this disease diagnosed in adulthood since it is a disease of children and adolescents. In addition, our patients had epileptic seizures, which were not previously documented in patients with CWF19L1 mutations. We postulate that mutations in this gene have widespread functional and structural changes in multiple levels of the neuraxis rather than being a pure cerebellar disorder.

中文翻译：

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晚发性常染色体隐性小脑性共济失调家族中 CWF19L1 基因的一个新变体 17

摘要

介绍

先前发表的研究表明，CWF19L1突变导致早发性常染色体隐性小脑共济失调 17。在本文中，我们报告了患有晚发性小脑共济失调伴癫痫的两姐妹的CWF19L1中的一种新型纯合错义变异，并描述了她们的临床和神经放射学发现.

方法

我们纳入了 MRI 结果支持的具有典型小脑性共济失调症状的两名女性患者。进行全外显子组测序（WES）数据分析以确定先证者的潜在遗传缺陷。桑格测序用于确认其他家庭成员中的变异。

结果

WES 揭示了 CWF19 样蛋白 1 中的纯合错义变异；CWF19L1基因c.395A>G；p.(Asp132Gly) (RefSeq NM_018294.4)。以前在文献中没有描述过这种变体。已知该基因的突变会导致常染色体隐性遗传疾病、脊髓小脑性共济失调、常染色体隐性遗传 17 (OMIM #616127)。

结论

总之，我们报告了CWF19L1中的一个新变异，作为两个常染色体隐性小脑共济失调姐妹的候选因果变异。这是来自阿拉伯国家的第一份报告。需要更多关于渐进性病程和成人发病患者的报告，但这可能是该疾病在成年期被诊断出的第一份报告，因为它是一种儿童和青少年疾病。此外，我们的患者有癫痫发作，这在CWF19L1突变患者中之前没有记录。我们假设该基因的突变在神经轴的多个水平上具有广泛的功能和结构变化，而不是纯粹的小脑疾病。