Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature
Year: 2013
Type: review
Study design: Observational Study
Abstract: 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.
DOI: 10.1002/ajmg.b.32148
Authors: Frédérique Béna, Damien L. Bruno, Mats Eriksson, Conny van Ravenswaaij‐Arts, Zornitza Stark, Trijnie Dijkhuizen, Erica Gerkes, Stefania Gimelli, Devika Ganesamoorthy, Ann Charlotte Thuresson, Audrey Labalme, Marianne Till, Frédéric Bilan, Laurent Pasquier, Alain Kitzis, Christele Dubourgm, Massimiliano Rossi, Armand Bottani, Maryline Gagnebin, Damien Sanlaville, Brigitte Gilbert‐Dussardier, Michel Guipponi, Arie van Haeringen, Marjolein Kriek, Claudia Ruivenkamp, Stylianos E. Antonarakis, Britt Marie Anderlid, Howard R. Slater, Jacqueline Schoumans
Institutions: University Hospital of Geneva, Royal Children's Hospital, The University of Melbourne, Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Karolinska Institutet, University Medical Center Groningen, University of Groningen, Uppsala University, Hospices Civils de Lyon, Université de Poitiers, Centre Hospitalier Universitaire de Poitiers, Centre Hospitalier Universitaire de Rennes, Lyon 1 Université, Centre National de la Recherche Scientifique, Inserm, Centre de Recherche en Neurosciences de Lyon, Leiden University Medical Center, University of Geneva, Centre Hospitalier Universitaire Vaudois
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2053952465