The authors have no conflicts of interest to declare.
Article first published online: 26 MAR 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 162, Issue 4, pages 388–403, June 2013
How to Cite
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. and Schoumans, J. (2013), Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature. Am. J. Med. Genet., 162: 388–403. doi: 10.1002/ajmg.b.32148
Frédérique Béna and Damien L. Bruno contributed equally to this work.
How to Cite this Article: Béna F, Bruno DL, Eriksson M, van Ravenswaaij-Arts C, Stark Z, Dijkhuizen T, Gerkes E, Gimelli S, Ganesamoorthy D, Thuresson AC, 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 SE, Anderlid BM, Slater HR, Schoumans J. 2013. Molecular and Clinical Characterization of 25 Individuals With Exonic Deletions of NRXN1 and Comprehensive Review of the Literature. Am J Med Genet Part B 162B:388–403.
- Issue published online: 25 MAY 2013
- Article first published online: 26 MAR 2013
- Manuscript Accepted: 22 FEB 2013
- Manuscript Received: 14 NOV 2012
- Victorian Government's Operational Infrastructure Support
- DHOS (Direction de l'Hospitalisation et de l'Organisation des Soins)
- University Hospital of Geneva, Swedish Research Council
- Karolinska Institutet
- University of Lausanne
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.