Phenotypic spectrum and genotype-phenotype correlations of NRXN1 exon deletions

Eur J Hum Genet. 2012 Dec;20(12):1240-7. doi: 10.1038/ejhg.2012.95. Epub 2012 May 23.

Abstract

Copy number variants (CNVs) and intragenic rearrangements of the NRXN1 (neurexin 1) gene are associated with a wide spectrum of developmental and neuropsychiatric disorders, including intellectual disability, speech delay, autism spectrum disorders (ASDs), hypotonia and schizophrenia. We performed a detailed clinical and molecular characterization of 24 patients who underwent clinical microarray analysis and had intragenic deletions of NRXN1. Seventeen of these deletions involved exons of NRXN1, whereas seven deleted intronic sequences only. The patients with exonic deletions manifested developmental delay/intellectual disability (93%), infantile hypotonia (59%) and ASDs (56%). Congenital malformations and dysmorphic features appeared infrequently and inconsistently among this population of patients with NRXN1 deletions. The more C-terminal deletions, including those affecting the β isoform of neurexin 1, manifested increased head size and a high frequency of seizure disorder (88%) when compared with N-terminal deletions of NRXN1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics
  • Adolescent
  • Adult
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Child
  • Child Development Disorders, Pervasive / diagnosis
  • Child Development Disorders, Pervasive / genetics
  • DNA Copy Number Variations
  • Exons / genetics*
  • Female
  • Gene Deletion*
  • Genotype*
  • Humans
  • Infant
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Introns
  • Male
  • Microarray Analysis
  • Muscle Hypotonia / congenital
  • Muscle Hypotonia / diagnosis
  • Muscle Hypotonia / genetics
  • Nerve Tissue Proteins / genetics*
  • Neural Cell Adhesion Molecules
  • Phenotype*
  • Protein Isoforms / genetics

Substances

  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal
  • NRXN1 protein, human
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules
  • Protein Isoforms