Genome-wide gene expression in a patient with 15q13.3 homozygous microdeletion syndrome

Eur J Hum Genet. 2013 Oct;21(10):1093-9. doi: 10.1038/ejhg.2013.1. Epub 2013 Jan 30.


We identified a novel homozygous 15q13.3 microdeletion in a young boy, with a complex neurodevelopmental disorder characterized by severe cerebral visual impairment with additional signs of congenital stationary night blindness, congenital hypotonia with areflexia, profound intellectual disability, and refractory epilepsy. The mechanisms by which the genes in the deleted region exert their effect are unclear. In this paper, we probed the role of downstream effects of the deletions as a contributing mechanism to the molecular basis of the observed phenotype. We analyzed gene expression of lymphoblastoid cells derived from peripheral blood of the proband and his relatives to ascertain the relative effects of the homozygous and heterozygous deletions. We identified 267 genes with apparent differential expression between the proband with the homozygous deletion and 3 age- and sex-matched typically developing controls. Several of the differentially expressed genes are known to influence neurodevelopment and muscular function, and thus may contribute to the observed cognitive impairment and hypotonia. We further investigated the role of CHRNA7 by measuring TNFα modulation (a potentially important pathway in regulating synaptic plasticity). We found that the cell line with the homozygous deletion lost the ability to inhibit the activation of tumor necrosis factor-α secretion. Our findings suggest downstream genes that may have been altered by the 15q13.3 homozygous deletion, and thus contributed to the severe developmental encephalopathy of the proband. Furthermore, we show that a potentially important pathway in learning and development is affected by the deletion of CHRNA7.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Child
  • Chromosome Deletion
  • Chromosome Disorders / diagnosis
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / metabolism
  • Chromosomes, Human, Pair 15 / genetics
  • Chromosomes, Human, Pair 15 / metabolism
  • Female
  • Genome, Human*
  • Homozygote*
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / metabolism
  • Male
  • Middle Aged
  • Pedigree
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Seizures / diagnosis
  • Seizures / genetics*
  • Seizures / metabolism
  • Transcriptome*
  • Tumor Necrosis Factor-alpha / metabolism
  • alpha7 Nicotinic Acetylcholine Receptor / genetics
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism


  • Chrna7 protein, human
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • alpha7 Nicotinic Acetylcholine Receptor

Supplementary concepts

  • Chromosome 15q13.3 Microdeletion Syndrome