NRXN1 deletions identified by array comparative genome hybridisation in a clinical case series – further understanding of the relevance of NRXN1 to neurodevelopmental disorders

Journal of Molecular Psychiatry

Caroline Mackie Ogilvie³  David A Collier²  Hannah Grayton²  Joo Wook Ahn³  Sarah Curran¹ 

[1] Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Kings College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK;MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK;Cytogenetics Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

关键词: Neurexins;    Microcephaly;    Epilepsy;    Neurodevelopmental disorders;    NRXN1;    Autism spectrum disorders;    Copy number variants;   

Others  :  820488
DOI  :  10.1186/2049-9256-1-4

 received in 2012-10-08, accepted in 2012-11-29,  发布年份 2013

【 摘 要 】

Background

Microdeletions in the NRXN1 gene have been associated with a range of neurodevelopmental disorders, including autism spectrum disorders, schizophrenia, intellectual disability, speech and language delay, epilepsy and hypotonia.

Results

In the present study we performed array CGH analysis on 10,397 individuals referred for diagnostic cytogenetic analysis, using a custom oligonucleotide array, which included 215 NRXN1 probes (median spacing 4.9 kb). We found 34 NRXN1 deletions (0.33% of referrals) ranging from 9 to 942 kb in size, of which 18 were exonic (0.17%). Three deletions affected exons also in the beta isoform of NRXN1. No duplications were found. Patients had a range of phenotypes including developmental delay, learning difficulties, attention deficit hyperactivity disorder (ADHD), autism, speech delay, social communication difficulties, epilepsy, behaviour problems and microcephaly. Five patients who had deletions in NRXN1 had a second CNV implicated in neurodevelopmental disorder: a CNTNAP2 and CSMD3 deletion in patients with exonic NRXN1 deletions, and a Williams-Beuren syndrome deletion and two 22q11.2 duplications in patients with intronic NRXN1 deletions.

Conclusions

Exonic deletions in the NRXN1 gene, predominantly affecting the alpha isoform, were found in patients with a range of neurodevelopmental disorders referred for diagnostic cytogenetic analysis. The targeting of dense oligonucleotide probes to the NRXN1 locus on array comparative hybridisation platforms provides detailed characterisation of deletions in this gene, and is likely to add to understanding of the importance of NRXN1 in neural development.

【 授权许可】

   
2013 Curran et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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