Splicing variant of WDR37 in a case of Neurooculocardiogenitourinary syndrome.
Cerebellar hypoplasia
Neurooculocardiogenitourinary syndrome
RT-PCR
Splicing
WDR37
Journal
Brain & development
ISSN: 1872-7131
Titre abrégé: Brain Dev
Pays: Netherlands
ID NLM: 7909235
Informations de publication
Date de publication:
02 Dec 2023
02 Dec 2023
Historique:
received:
18
08
2023
revised:
18
10
2023
accepted:
26
11
2023
medline:
4
12
2023
pubmed:
4
12
2023
entrez:
3
12
2023
Statut:
aheadofprint
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
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
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.
CONCLUSION
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.
Identifiants
pubmed: 38044197
pii: S0387-7604(23)00177-8
doi: 10.1016/j.braindev.2023.11.007
pii:
doi:
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.