Characterization of an unbalanced translocation causing 3q28qter duplication and 10q26.2qter deletion in a patient with global developmental delay and self-injury

Cold Spring Harb Mol Case Stud. 2020 Dec 17;6(6):a005884. doi: 10.1101/mcs.a005884. Print 2020 Dec.


Chromosomal structural variation can cause severe neurodevelopmental and neuropsychiatric phenotypes. Here we present a nonverbal female adolescent with severe stereotypic movement disorder with severe problem behavior (e.g., self-injurious behavior, aggression, and disruptive and destructive behaviors), autism spectrum disorder, severe intellectual disability, attention deficit hyperactivity disorder, and global developmental delay. Previous cytogenetic analysis revealed balanced translocations present in the patient's apparently normal mother. We hypothesized the presence of unbalanced translocations in the patient due to maternal history of spontaneous abortions. Whole-genome sequencing and whole-genome optical mapping, complementary next-generation genomic technologies capable of the accurate and robust detection of structural variants, identified t(3;10), t(10;14), and t(3;14) three-way balanced translocations in the mother and der(10)t(3;14;10) and der(14)t(3;14;10) translocations in the patient. Instead of a t(3;10), she inherited a normal maternal copy of Chromosome 3, resulting in an unbalanced state of a 3q28qter duplication and 10q26.2qter deletion. Copy-imbalanced genes in one or both of these regions, such as DLG1, DOCK1, and EBF3, may contribute to the patient's phenotype that spans neurodevelopmental, musculoskeletal, and psychiatric domains, with the possible contribution of a maternally inherited 15q13.2q13.3 deletion.

Keywords: attention deficit hyperactivity disorder; autism; intellectual disability, severe; language impairment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Autism Spectrum Disorder / genetics
  • Autistic Disorder / genetics
  • Chromosome Deletion*
  • Discs Large Homolog 1 Protein
  • Female
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / therapy
  • Nervous System Malformations / genetics*
  • Phenotype
  • Self-Injurious Behavior*
  • Specific Language Disorder / genetics
  • Transcription Factors
  • Translocation, Genetic*
  • Whole Genome Sequencing
  • rac GTP-Binding Proteins


  • DLG1 protein, human
  • DOCK1 protein, human
  • Discs Large Homolog 1 Protein
  • EBF3 protein, human
  • Transcription Factors
  • rac GTP-Binding Proteins