背景：尿路综合征（NOCGUS），以运动障碍为特征的多系统综合征，智力残疾,癫痫发作,大脑结构异常,眼部疾病,和心脏疾病，已报道在人类中具有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中NOCGUS的原因。
方法：我们确定了WDR37的从头内含子4-bp缺失，c.727-27_727-24del，SpliceAI预测会导致异常剪接，患有NOCGUS的患者。逆转录聚合酶链反应（RT-PCR）显示信使RNA中外显子10之前的内含子保留了63个碱基对，预计会插入21个额外的异常氨基酸（p。S242_I243inLCQKLKLKISRKCLFWPSLWQQ)。病人有新的表型，肛门闭锁,多囊肾，除了智力残疾，癫痫发作,小脑Vermian异常,和结肠瘤，这是典型的NOCGUS。我们没有观察到运动障碍或心血管异常。
结论：这是首例报道的具有WDR37剪接变体的NOCGUS病例，表现出独特但可变的特征。我们的发现可能会扩展NOCGUS的可能表型表达。
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.
METHODS: 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.
CONCLUSIONS: 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.
