A de novo microdeletion in NRXN1 in a Dutch patient with mild intellectual disability, microcephaly and gonadal dysgenesis

Genet Res (Camb). 2015 Oct 6:97:e19. doi: 10.1017/S001667231500021X.

Abstract

This report is regarding a Dutch female with microcephaly, mild intellectual disability (ID), gonadal dysgenesis and dysmorphic facial features with synophrys. Upon genotyping, an ~455 kb de novo deletion encompassing the first exon of NRXN1 was found. Bidirectional sequencing of the coding exons of the NRXN1 alpha isoform was subsequently performed to investigate the possibility of a pathogenic mutation on the other allele, but we could not find any other mutation. Previously, many heterozygous mutations as well as microdeletions in NRXN1 were shown to be associated with ID, autism, schizophrenia, and other psychiatric and psychotic disorders. Our results are in agreement with other reports that show that NRXN1 deletions can lead to ID, microcephaly and mild dysmorphic features. However, this is the first report of gonadal dysgenesis being associated with such deletions. It is not clear whether there is a causal relationship between the NRXN1 deletion and gonadal dysgenesis, but it is of interest that the FSHR gene, which encodes the follicle-stimulating hormone receptor causative correlation that is mutated in ovarian dysgenesis, is located proximal to the NRXN1 gene. Given that most of the females carrying NRXN1 deletions have been diagnosed at a prepubertal age, gynecologic screening of female carriers of a NRXN1 deletion is warranted.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adult
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Chromosome Deletion
  • Chromosomes, Human, Pair 2 / genetics
  • Female
  • Gene Deletion*
  • Gonadal Dysgenesis*
  • Humans
  • Intellectual Disability*
  • Microcephaly*
  • Nerve Tissue Proteins / genetics*
  • Netherlands
  • Neural Cell Adhesion Molecules
  • Receptors, FSH / genetics

Substances

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