Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature123. Issue 4 (26th March 2013)

• Record Type: Journal Article
• Authors: Béna, Frédérique; Bruno, Damien L.; Eriksson, Mats; van Ravenswaaij‐Arts, Conny; Stark, Zornitza; Dijkhuizen, Trijnie; Gerkes, Erica; Gimelli, Stefania; Ganesamoorthy, Devika; Thuresson, Ann Charlotte; Labalme, Audrey; Till, Marianne; Bilan, Frédéric; Pasquier, Laurent; Kitzis, Alain; Dubourgm, Christele; Rossi, Massimiliano; Bottani, Armand; Gagnebin, Maryline; Sanlaville, Damien; Gilbert‐Dussardier, Brigitte; Guipponi, Michel; van Haeringen, Arie; Kriek, Marjolein; Ruivenkamp, Claudia; Antonarakis, Stylianos E.; Anderlid, Britt Marie; Slater, Howard R.; Schoumans, Jacqueline
• Is Part Of: American journal of medical genetics. Volume 162:Issue 4(2013)
• Page Start: 388
• Page End: 403
• Publication Date: 2013-03-26
• Subjects: Neuropsychiatry -- Periodicals; Medical genetics -- Periodicals; 616.8904205
• DOI: 10.1002/ajmg.b.32148
• Languages: English
• ISSNs: 1552-4841

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>This study aimed to elucidate the observed variable phenotypic expressivity associated with <italic>NRXN1</italic> (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with <italic>NRXN1</italic> 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 <italic>NRXN1</italic> 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 <italic>NRXN1</italic>‐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 <italic>NRXN1</italic>. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of <italic>NRXN1</italic> 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.</p> </abstract>