Affiliation:
1. Showa University School of Medicine
2. Hamamatsu University School of Medicine
3. Kanagawa Children’s Medical Center
Abstract
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 neurooculocardiogenitourinary syndrome (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.
Publisher
Research Square Platform LLC
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