NURR1 mutations in cases of schizophrenia and manic-depressive disorder

Transgenic mice lacking the nuclear orphan transcription factor Nur-related receptor 1 (Nurr1) fail to develop mesencephalic dopamine neurons. There i s a highly homologous NURR1 gene in humans (formerly known as NOT) which th erefore constitutes a good candidate gene for neurologic and psychiatric di sorders with an involvement of the dopamine neuron system, such as Parkinso n's disease, schizophrenia, and manic-depression. By direct sequencing of g enomic DNA, we found two different missense mutations in the third exon of NURR1 in two schizophrenic patients and another missense mutation in the sa me exon in an individual with manic-depressive disorder. All three mutation s caused a similar reduction of in vitro transcriptional activity of NURR1 dimers of about 30-40%. Neither of these amino acid changes, nor any sequen ce changes whatsoever, were found in patients with Parkinson's disease or c ontrol DNA material of normal populations. (C) 2000 Wiley Liss, Inc.