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Disruption of a brain transcription factor, NPAS3, is associated with schizophrenia and learning disability
Author(s) -
Pickard Ben S.,
Malloy M.P.,
Porteous D.J.,
Blackwood D.H.R.,
Muir W.J.
Publication year - 2005
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30204
Subject(s) - cosmid , genetics , locus (genetics) , biology , gene , chromosomal translocation
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. © 2005 Wiley‐Liss, Inc.