Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature. - Archive ouverte HAL Access content directly
Journal Articles American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Year : 2013

Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.

Damien L Bruno
  • Function : Author
Mats Eriksson
  • Function : Author
Devika Ganesamoorthy
  • Function : Author
Christele Dubourgm
  • Function : Author
Massimiliano Rossi
  • Function : Author
Maryline Gagnebin
  • Function : Author
Brigitte Gilbert-Dussardier
  • Function : Author
Michel Guipponi
  • Function : Author
Marjolein Kriek
  • Function : Author
Stylianos E Antonarakis
  • Function : Author
Jacqueline Schoumans
  • Function : Author

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.

Dates and versions

hal-01120394 , version 1 (25-02-2015)

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Frédérique Béna, Damien L Bruno, Mats Eriksson, Conny van Ravenswaaij-Arts, Zornitza Stark, et al.. Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2013, 162B (4), pp.388-403. ⟨10.1002/ajmg.b.32148⟩. ⟨hal-01120394⟩
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