Disruption of a brain transcription factor, NPAS3, is associated with schizophrenia and learning disability
Abstract
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.
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Disruption of NPAS3 by a reciprocal translocation in chromosome 14q13 was reported in a family with intellectual disability and schizophrenia.
“Disruption of NPAS3 by a reciprocal translocation in chromosome 14q13 was reported in a family with intellectual disability and schizophrenia (Kamnasaran et al. 2003; Pickard et al. 2005)”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Pickard et al. 2005
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“In addition, family and association studies have identified NPAS3 as a candidate gene for schizophrenia in families (Kamnasaran et al. 2003; Pickard et al. 2005, 2006) and association studies (Pickard et al. 2009; Huang et al. 2010).”
BackgroundInfluential
- Authors
- Pickard, B. S., Malloy, M. P., Porteous, D. J., Blackwood, D. H. R., & Muir, W. J.
- Affiliations
- Western General Hospital (GB)
- Royal Edinburgh Hospital (GB)
- Corresponding author
- Pickard, Ben S.
- Venue
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2005
- Volume
- 136B
- Issue
- 1
- Pages
- 26-32
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2070465681
- Cited by
- 89
- References
- 31
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- NPAS3, schizophrenia, learning disabilities, bHLH-PAS transcription factors, dominant negative effect, Fahr disease, psychosis, familial schizophrenia, gene disruption
- MeSH terms
- Abnormalities, Multiple, Amino Acid Sequence, Base Sequence, Brain, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 9, Family Health, Female, Humans, Learning Disabilities, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Schizophrenia, Transcription Factors, Translocation, Genetic, In Situ Hybridization, Fluorescence, Chromosome Breakage, Chromosome Disorders, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors
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