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Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature
Open accessAbstract
This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1 ‐deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the β‐isoform of neurexin‐1 and increased head size, as was recently published in four cases with a deletion involving the C‐terminus of NRXN1 . We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders. © 2013 Wiley Periodicals, Inc.
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“De novo CNVs are observed in 5%–10% of screened ASD-affected individuals, and after further follow-up studies, some of them have proven to alter high-risk genes (e.g., NRXN112 [MIM 600565]).”
From Convergence of genes and cellular pathways dysregulated in autism spectrum disorders (2014) · cites this paper as [12]
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Convergence of genes and cellular pathways dysregulated in autism spectrum disorders
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Metadata
- Authors
- Béna, F., Bruno, D. L., Eriksson, M., van Ravenswaaij‐Arts, C., Stark, Z., Dijkhuizen, T., Gerkes, E., Gimelli, S., Ganesamoorthy, D., Thuresson, A. C., Labalme, A., Till, M., Bilan, F., Pasquier, L., Kitzis, A., Dubourgm, C., Rossi, M., Bottani, A., Gagnebin, M., Sanlaville, D., Gilbert‐Dussardier, B., Guipponi, M., van Haeringen, A., Kriek, M., Ruivenkamp, C., Antonarakis, S. E., Anderlid, B. M., Slater, H. R., & Schoumans, J.
- Affiliations
- Royal Children's Hospital (AU)
- Karolinska Institutet (SE)
- University Medical Center Groningen (NL)
- University Hospital of Geneva (CH)
- Uppsala University (SE)
- Hospices Civils de Lyon (FR)
- Université de Poitiers (FR)
- Centre Hospitalier Universitaire de Rennes (FR)
- Lyon 1 Université (FR)
- Leiden University Medical Center (NL)
- University of Geneva (CH)
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Schoumans, Jacqueline
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2013-03-26
- Volume
- 162
- Issue
- 4
- Pages
- 388-403
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2053952465
- Cited by
- 109
- References
- 49
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 10 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 15 · 2014: 18 · 2013: 5
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- green
- research.rug.nl
- Licence
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- IRIS (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- NRXN1, exon deletion, haploinsufficiency, copy number variation, intellectual disability, language delay, autism spectrum disorder, seizures, hypotonia, phenotypic variability, neurodevelopmental disorders, head size
- MeSH terms
- Autistic Disorder, Calcium-Binding Proteins, Exons, Heterozygote, Humans, Karyotyping, Nerve Tissue Proteins, Seizures, Cohort Studies, Cell Adhesion Molecules, Neuronal, Sequence Deletion, Neural Cell Adhesion Molecules
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