Splicing variant of WDR37 in a case of Neurooculocardiogenitourinary syndrome

IF 1.4 4区 医学 Q4 CLINICAL NEUROLOGY
Mai Samejima , Mitsuko Nakashima , Jun Shibasaki , Hirotomo Saitsu , Mitsuhiro Kato
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引用次数: 0

Abstract

Background

Neurooculocardiogenitourinary syndrome (NOCGUS), a multisystemic syndrome characterized by motor disorder, intellectual disability, seizures, abnormal brain structure, ocular diseases, and cardiac diseases, has been reported with missense variant of WD repeat-containing protein 37 (WDR37) in humans. This report aimed to identify the cause of NOCGUS in an affected patient.

Case presentation

We identified a de novo intronic 4-bp deletion of WDR37, c.727-27_727-24del, which were predicted to cause abnormal splicing by SpliceAI, in the patient with NOCGUS. Reverse transcription polymerase chain reaction (RT-PCR) revealed intron retention of 63 base pairs before exon 10 in messenger RNA, which was predicted to insert 21 additional aberrant amino acids (p.S242_I243insLCQKKLKISRKCLFWPSLWQQ). The patient had novel phenotypes, anal atresia, and polycystic kidney, in addition to intellectual disability, seizures, cerebellar vermian anomaly, and coloboma, which are typical in NOCGUS. We did not observe motor impairments or cardiovascular anomalies.

Conclusion

This is the first reported case of NOCGUS with the splicing variant of WDR37, which manifests with distinctive but variable features. Our findings may expand a possible phenotypic expression of NOCGUS.

WDR37剪接变异体在神经-心-生殖-泌尿综合征中的表现。
背景:神经-心-泌尿系统综合征(NOCGUS)是一种以运动障碍、智力残疾、癫痫发作、脑结构异常、眼部疾病和心脏疾病为特征的多系统综合征,已报道人类WD重复蛋白37 (WDR37)错义变异。本报告旨在确定在受影响的病人nogus的原因。病例介绍:我们在nogus患者中发现了一个新的内含子4 bp缺失WDR37, c.727-27_727-24del,该缺失被预测会导致SpliceAI的异常剪接。逆转录聚合酶链反应(RT-PCR)显示,在信使RNA的第10号外显子前,内含子保留了63个碱基对,预计会插入21个异常氨基酸(p.S242_I243insLCQKKLKISRKCLFWPSLWQQ)。该患者有新的表型,肛门闭锁和多囊肾,此外还有智力残疾、癫痫发作、小脑蠕虫异常和结肠瘤,这些都是nogus的典型特征。我们没有观察到运动障碍或心血管异常。结论:这是首次报道的WDR37剪接变异体nogus病例,该病例表现出独特但多变的特征。我们的发现可能扩大了nogus可能的表型表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Brain & Development
Brain & Development 医学-临床神经学
CiteScore
3.60
自引率
0.00%
发文量
153
审稿时长
50 days
期刊介绍: Brain and Development (ISSN 0387-7604) is the Official Journal of the Japanese Society of Child Neurology, and is aimed to promote clinical child neurology and developmental neuroscience. The journal is devoted to publishing Review Articles, Full Length Original Papers, Case Reports and Letters to the Editor in the field of Child Neurology and related sciences. Proceedings of meetings, and professional announcements will be published at the Editor''s discretion. Letters concerning articles published in Brain and Development and other relevant issues are also welcome.
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