DOPAMINE D4 RECEPTOR VARIANT IN AFRICANS, D4(VALINE194GLYCINE), IS INSENSITIVE TO DOPAMINE AND CLOZAPINE - REPORT OF A HOMOZYGOUS INDIVIDUAL

The D4(Valine194Glycine) receptor is a variant of the dopamine D4 rece ptor and is found in 12.5% of the Afro-Caribbean population, Glycine r eplaces valine at a position one amino acid away from a serine which i s critical for the attachment of dopamine, To determine whether this m utation had an effect on the properties of the dopamine D4 receptor, w e constructed this variant and tested the sensitivity of the expressed protein with various drugs, We found that the variant receptor was tw o orders of magnitude less sensitive to dopamine, clozapine and olanza pine, The variant receptor was insensitive to guanine nucleotide, indi cating the absence of a high-affinity state or functional state, The o ne 15-year-old individual found homozygous for this variant also had s ickle cell disease, The patient revealed an overall pattern of low wei ght and no axillary or pubic hair. (C) 1996 Wiley-Liss, Inc.