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

• Published in: BMC medical genetics 2018-11, Vol.19 (1), p.197-197, Article 197
• Main Authors: Mavros, Chrystal F, Brownstein, Catherine A, Thyagrajan, Roshni, Genetti, Casie A, Tembulkar, Sahil, Graber, Kelsey, Murphy, Quinn, Cabral, Kristin, VanNoy, Grace E, Bainbridge, Matthew, Shi, Jiahai, Agrawal, Pankaj B, Beggs, Alan H, D'Angelo, Eugene, Gonzalez-Heydrich, Joseph
• Format: Article
• Language: English
• Subjects: 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; Bipolar disorder; Case Report; Case reports; Case studies; Child; Childhood onset psychosis; Children; Chromatin remodeling; DNA damage; DNA methylation; DNA repair; Exome Sequencing; Gene Expression; Genetic aspects; Genomics; Genotype; Genotypes; Health aspects; Heredity; Humans; Kinases; Learning Disabilities - diagnosis; Learning Disabilities - genetics; Learning Disabilities - physiopathology; Major depression with psychotic features; Male; Mendelian Randomization Analysis; Mental depression; Mental disorders; Models, Molecular; Mutation; Nonverbal learning disabilities; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Obsessive compulsive disorder; Obsessive-Compulsive Disorder - diagnosis; Obsessive-Compulsive Disorder - genetics; Obsessive-Compulsive Disorder - physiopathology; Pediatric diseases; Phenotype; Point Mutation; Protein Conformation; Protein kinase; Protein kinases; Psychosis; Psychotic Disorders - diagnosis; Psychotic Disorders - genetics; Psychotic Disorders - physiopathology; Schizophrenia; Single nucleotide polymorphisms; Very early onset psychosis
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-018-0711-9

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. 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. 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.