De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome

Am J Med Genet A. 2017 Jun;173(6):1656-1662. doi: 10.1002/ajmg.a.38171. Epub 2017 Apr 13.

Abstract

Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al. (2011) Neuron 70: 863-885]. Many chromosomal abnormalities, including sub microscopic genomic deletions and duplications, are missed by G-banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al. (2010) Pediatrics 125: e727-735]. Translocations involving chromosomes 4 and 8 are possibly the second most frequent translocation in humans and are often undetected in routine cytogenetics [Giglio et al. (2002) Circulation 102: 432-437]. Deletions of 4p16 have been associated with Wolf-Hirschhorn syndrome while 4p16 duplications have been associated with an overgrowth syndrome and mild to moderate mental retardation [Partington et al. (1997) Journal of Medical Genetics 34: 719-728]. The 8p23.3 region contains the autism candidate gene DLGAP2, which can contribute to autism when disrupted [Marshall et al. (2008) The American Journal of Human Genetics 82: 477-488] . There has been a case report of a family with autism spectrum disorder (ASD), prominent obsessional behavior, and overgrowth in patients with der (8) t (4;8) p (16;23) [Partington et al. (1997)]. This is an independent report of a male patient with autism, obsessive compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo unbalanced translocation der (8) t (4;8) p (16.1→ter; 23.1→ter) was initially missed by routine cytogenetics but detected with SNP microarray, allowing higher resolution of translocation breakpoints.

Keywords: 4p duplication; 8p deletion; ADHD; autism; der (8) t (4;8); obsessive compulsive disorder; overgrowth syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / pathology
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 4 / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Karyotyping
  • Male
  • Obsessive-Compulsive Disorder / genetics*
  • Obsessive-Compulsive Disorder / physiopathology
  • Translocation, Genetic / genetics*
  • Wolf-Hirschhorn Syndrome / genetics
  • Wolf-Hirschhorn Syndrome / physiopathology