Dysbindin (DTNBP1, 6p22.3) is associated with childhood-onset psychosis and endophenotypes measured by the Premorbid Adjustment Scale (PAS)

J Autism Dev Disord. 2005 Dec;35(6):831-8. doi: 10.1007/s10803-005-0028-3.

Abstract

Straub et al. (2002) recently identified the 6p22.3 gene dysbindin (DTNBP1) through positional cloning as a schizophrenia susceptibility gene. We studied a rare cohort of 102 children with onset of psychosis before age 13. Standardized ratings of early development, medication response, neuropsychological and cognitive performance, premorbid dysfunction and clinical follow-up were obtained. Fourteen SNPs were genotyped in the gene DTNBP1. Family-based pairwise and haplotype transmission disequilibrium test (TDT) analysis with the clinical phenotype, and quantitative transmission disequilibrium test (QTDT) explored endophenotype relationships. One SNP was associated with diagnosis (TDT p=.01). The QTDT analyses showed several significant relationships. Four adjacent SNPs were associated (p values=.0009-.003) with poor premorbid functioning. These findings support the hypothesis that this and other schizophrenia susceptibility genes contribute to early neurodevelopmental impairment.

MeSH terms

  • Adolescent
  • Age of Onset
  • Alleles
  • Carrier Proteins / genetics*
  • Child
  • Chromosomes, Human, Pair 6 / genetics*
  • Cohort Studies
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Linkage Disequilibrium / genetics
  • Phenotype*
  • Psychotic Disorders / genetics*
  • Schizophrenia / genetics*
  • Social Adjustment*
  • Surveys and Questionnaires*

Substances

  • Carrier Proteins
  • DTNBP1 protein, human
  • Dysbindin
  • Dystrophin-Associated Proteins