A mother and daughter diagnosed with schizophrenia and schizophrenia co-morbid with mild learning disability, respectively, possess a balanced reciprocal translocation t(9,14)(q34.2;q13). Fluorescence in situ hybridization (FISH) with YAC, BAC, and cosmid probes indicate that the chromosome 14q13 breakpoint disrupts a large gene, NPAS3, encoding a CNS expressed transcription factor of the basic helix-loop-helix PAS (bHLH-PAS) gene family. By analogy with other members of the bHLH-PAS family, the putative truncated protein generated from the disrupted gene locus may have a dominant negative effect. The 14q13 region was previously identified by a linkage study of an inherited neurodegenerative condition, idiopathic basal ganglia calcification (IBGC or Fahr syndrome, OMIM:213600/606656), which is often co-morbid with psychosis. Sequencing of the gene in a third patient diagnosed with IBGC, schizophrenia, and mild learning disability did not reveal functional mutations.
|Number of pages||7|
|Journal||American Journal of Medical Genetics Part B: Neuropsychiatric Genetics|
|Publication status||Published - 2005|
- Abnormalities, Multiple/*genetics/pathology Amino Acid Sequence Base Sequence Brain/metabolism Chromosome Breakage/genetics Chromosome Disorders/genetics/pathology Chromosomes, Human, Pair 14/genetics Chromosomes, Human, Pair 9/genetics Family Health Female Humans In Situ Hybridization, Fluorescence Learning Disorders/*pathology Molecular Sequence Data *Mutation Nerve Tissue Proteins/*genetics Schizophrenia/*pathology Transcription Factors/*genetics *Translocation, Genetic