STRUCTURAL-CHANGE IN DOPAMINE D-2 RECEPTOR GENE IN A PATIENT WITH NEUROLEPTIC MALIGNANT SYNDROME

Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome, Therefore, we examined the complete coding sequences of the dopamine D-2 receptor (DRD2) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS, Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequence differences, We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG-->TCG) of exon 7 of the DRD2 gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. (C) 1995 Wiley-Liss, Inc.