Journal article
De novo variants of NR4A2 are associated with neurodevelopmental disorder and epilepsy
Genetics in medicine, Vol.22(8), pp.1413-1417
08/2020
DOI: 10.1038/s41436-020-0815-4
PMCID: PMC7394879
PMID: 32366965
Abstract
This study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in the NR4A2 gene.
Variants were identified and de novo origins were confirmed through trio exome sequencing in all but one patient. Targeted RNA sequencing was performed for one variant to confirm its splicing effect. Independent discoveries were shared through GeneMatcher.
Missense and loss-of-function variants in NR4A2 were identified in patients from eight unrelated families. One patient carried a larger deletion including adjacent genes. The cases presented with developmental delay, hypotonia (six cases), and epilepsy (six cases). De novo status was confirmed for eight patients. One variant was demonstrated to affect splicing and result in expression of abnormal transcripts likely subject to nonsense-mediated decay.
Our study underscores the importance of NR4A2 as a disease gene for neurodevelopmental disorders and epilepsy. The identified variants are likely causative of the seizures and additional developmental phenotypes in these patients.
Details
- Title: Subtitle
- De novo variants of NR4A2 are associated with neurodevelopmental disorder and epilepsy
- Creators
- Sakshi Singh - University Medical Center UtrechtAditi Gupta - Mayo Clinic Rochester, MNMichael Zech - Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.Ashley N Sigafoos - Mayo Clinic Rochester, MNKarl J Clark - Mayo ClinicYasemin Dincer - Technical University of MunichMatias Wagner - Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.Jennifer B Humberson - University of VirginiaSarah Green - University of Arkansas for Medical SciencesKoen van Gassen - Department of Genetics, University Medical Centre Utrecht, Utrecht, The NetherlandsTracy Brandt - GeneDxRhonda E Schnur - GeneDxFrancisca Millan - GeneDxYue Si - GeneDxVolker Mall - Technical University of MunichJuliane Winkelmann - Helmholtz Zentrum MünchenRalitza H Gavrilova - Departments of Clinical Genomics and Neurology, Mayo Clinic, Rochester, MN, USA.Eric W Klee - Mayo ClinicKendra Engleman - University of Missouri–Kansas CityNicole P Safina - University of Missouri–Kansas CityRachel Slaugh - Washington University in St. LouisEmily M Bryant - Lurie Children's HospitalWen-Hann Tan - Harvard UniversityJorge Granadillo - Washington University in St. LouisSunita N Misra - Lurie Children's HospitalG Bradley Schaefer - University of Arkansas for Medical SciencesShelley Towner - University of VirginiaEva H Brilstra - University Medical Center UtrechtBobby P C Koeleman - University Medical Center Utrecht
- Resource Type
- Journal article
- Publication Details
- Genetics in medicine, Vol.22(8), pp.1413-1417
- DOI
- 10.1038/s41436-020-0815-4
- PMID
- 32366965
- PMCID
- PMC7394879
- NLM abbreviation
- Genet Med
- ISSN
- 1098-3600
- eISSN
- 1530-0366
- Language
- English
- Date published
- 08/2020
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984354150102771
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