De novo variant of TRRAP in a patient with very early onset psychosis in the context of non-verbal learning disability and obsessive-compulsive disorder: a case report

BMC Med Genet. 2018 Nov 13;19(1):197. doi: 10.1186/s12881-018-0711-9.

Abstract

Background: TRRAP encodes a multidomain protein kinase that works as a genetic cofactor to influence DNA methylation patterns, DNA damage repair, and chromatin remodeling. TRRAP protein is vital to early neural developmental processes, and variants in this gene have been associated with schizophrenia and childhood disintegrative disorder.

Case presentation: Here, we report on a patient with a de novo nonsynonymous TRRAP single-nucleotide variant (EST00000355540.3:c.5957G > A, p.Arg1986Gln) and early onset major depression accompanied by a psychotic episode (before age 10) that occurred in the context of longer standing nonverbal learning disability and a past history of obsessions and compulsions.

Conclusions: The de novo variant and presentation of very early onset psychosis indicate a rare Mendelian disorder inheritance model. The genotype and behavioral abnormalities of this patient are reviewed.

Keywords: Childhood onset psychosis; Major depression with psychotic features; Obsessive compulsive disorder; Psychosis; Very early onset psychosis.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Age of Onset
  • Autism Spectrum Disorder / diagnosis
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / physiopathology
  • Child
  • Exome Sequencing
  • Gene Expression
  • Genotype
  • Humans
  • Learning Disabilities / diagnosis
  • Learning Disabilities / genetics*
  • Learning Disabilities / physiopathology
  • Male
  • Mendelian Randomization Analysis
  • Models, Molecular
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Obsessive-Compulsive Disorder / diagnosis
  • Obsessive-Compulsive Disorder / genetics*
  • Obsessive-Compulsive Disorder / physiopathology
  • Phenotype
  • Point Mutation*
  • Protein Conformation
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / genetics*
  • Psychotic Disorders / physiopathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Nuclear Proteins
  • transformation-transcription domain-associated protein