Phenotypic consequences of gene disruption by a balanced de novo translocation involving SLC6A1 and NAA15

Eur J Med Genet. 2018 Oct;61(10):596-601. doi: 10.1016/j.ejmg.2018.03.013. Epub 2018 Apr 3.

Abstract

Mapping of de novo balanced chromosomal translocations (BCTs) in patients with sporadic poorly characterized disease(s) is an unbiased method of finding candidate gene(s) responsible for the observed symptoms. We present a paediatric patient suffering from epilepsy, developmental delay (DD) and atrial septal defect IIº (ASD) requiring surgery. Karyotyping indicated an apparently balanced de novo reciprocal translocation 46,XX,t(3;4)(p25.3;q31.1), whereas aCGH did not reveal any copy number changes. Using shallow mate-pair whole genome sequencing and direct Sanger sequencing of breakpoint regions we found that translocation disrupted SLC6A1 and NAA15 genes. Our results confirm two previous reports indicating that loss of function of a single allele of SLC6A1 causes epilepsy. In addition, we extend existing evidence that disruption of NAA15 is associated with DD and with congenital heart defects.

Keywords: De novo balanced chromosomal translocations; Developmental disability; NAA15; SLC6A1; Shallow mate-pair whole genome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Child, Preschool
  • Chromosome Breakpoints
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • GABA Plasma Membrane Transport Proteins / genetics*
  • Humans
  • Infant
  • N-Terminal Acetyltransferase A / genetics*
  • N-Terminal Acetyltransferase E / genetics*
  • Phenotype
  • Translocation, Genetic*

Substances

  • GABA Plasma Membrane Transport Proteins
  • NAA15 protein, human
  • SLC6A1 protein, human
  • N-Terminal Acetyltransferase A
  • N-Terminal Acetyltransferase E