NURR1 mutations in cases of schizophrenia and manic-depressive disorder

Am J Med Genet. 2000 Dec 4;96(6):808-13. doi: 10.1002/1096-8628(20001204)96:6<808::aid-ajmg23>;2-e.


Transgenic mice lacking the nuclear orphan transcription factor Nur-related receptor 1 (Nurr1) fail to develop mesencephalic dopamine neurons. There is a highly homologous NURR1 gene in humans (formerly known as NOT) which therefore constitutes a good candidate gene for neurologic and psychiatric disorders with an involvement of the dopamine neuron system, such as Parkinson's disease, schizophrenia, and manic-depression. By direct sequencing of genomic DNA, we found two different missense mutations in the third exon of NURR1 in two schizophrenic patients and another missense mutation in the same exon in an individual with manic-depressive disorder. All three mutations caused a similar reduction of in vitro transcriptional activity of NURR1 dimers of about 30-40%. Neither of these amino acid changes, nor any sequence changes whatsoever, were found in patients with Parkinson's disease or control DNA material of normal populations. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:808-813, 2000.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Bipolar Disorder / genetics*
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • DNA-Binding Proteins*
  • Gene Frequency
  • Humans
  • Mutation
  • Mutation, Missense
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Schizophrenia / genetics*
  • Sequence Deletion
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • NR4A2 protein, human
  • Nr4a2 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Transcription Factors
  • DNA