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.

中文翻译：

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神经眼心泌尿生殖综合征病例中 WDR37 的剪接变异

背景

神经眼心生殖泌尿综合征 (NOCGUS) 是一种多系统综合征，其特征为运动障碍、智力障碍、癫痫、脑结构异常、眼部疾病和心脏病，据报道人类存在 WD 重复序列蛋白 37 (WDR37) 的错义变体。本报告旨在确定受影响患者出现 NOCGUS 的原因。

案例展示

我们在 NOCGUS 患者中发现了WDR37的从头内含子 4-bp 缺失（c.727-27_727-24del），SpliceAI 预测该缺失会导致 NOCGUS 患者的异常剪接。逆转录聚合酶链反应 (RT-PCR) 显示信使 RNA 中外显子 10 之前保留了 63 个碱基对的内含子，预计该内含子会插入 21 个额外的异常氨基酸 (p.S242_I243insLCQKKKLKISRKCLFWPSLWQQ)。该患者具有新的表型、肛门闭锁和多囊肾，此外还有智力障碍、癫痫发作、小脑蚓部异常和缺损，这些都是 NOCGUS 的典型症状。我们没有观察到运动障碍或心血管异常。

结论

这是首例报道的带有WDR37剪接变体的 NOCGUS 病例，其表现出独特但可变的特征。我们的研究结果可能会扩大 NOCGUS 可能的表型表达。