Disruption of a brain transcription factor, NPAS3, is associated with schizophrenia and learning disability.

摘要: A mother and daughter diagnosed with schizophrenia co-morbid mild learning disability, respectively, possess a balanced reciprocal translocation t(9,14)(q34.2;q13). Fluorescence in situ hybridization (FISH) YAC, BAC, cosmid probes indicate that the chromosome 14q13 breakpoint disrupts large gene, NPAS3, encoding CNS expressed transcription factor of basic helix-loop-helix PAS (bHLH-PAS) gene family. By analogy other members bHLH-PAS family, putative truncated protein generated from disrupted locus may have dominant negative effect. The region was previously identified by linkage study an inherited neurodegenerative condition, idiopathic basal ganglia calcification (IBGC or Fahr syndrome, OMIM:213600/606656), which is often psychosis. Sequencing third patient IBGC, schizophrenia, disability did not reveal functional mutations.