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Title

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

Authors
Bruno, Damien L
Eriksson, Mats
van Ravenswaaij-Arts, Conny
Stark, Zornitza
Dijkhuizen, Trijnie
Gerkes, Erica
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Published in American Journal of Medical Genetics. B. 2013, vol. 162, no. 4, p. 388-403
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.
Keywords Autistic Disorder/geneticsCell Adhesion Molecules, Neuronal/geneticsCohort StudiesExonsHeterozygoteHumansKaryotypingNerve Tissue Proteins/geneticsSeizures/geneticsSequence Deletion
Identifiers
PMID: 23533028
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Article (Published version) (27.7 MB) - document accessible for UNIGE members only Limited access to UNIGE
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Research group Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
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SLOAN BENA, Frédérique et al. Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature. In: American Journal of Medical Genetics. B, 2013, vol. 162, n° 4, p. 388-403. https://archive-ouverte.unige.ch/unige:34630

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Deposited on : 2014-03-05

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