Liu I S, Seeman P, Sanyal S, Ulpian C, Rodgers-Johnson P E, Serjeant G R, Van Tol H H
Department of Pharmacology, Medical Sciences Building, Canada.
Am J Med Genet. 1996 Jan 22;61(3):277-82. doi: 10.1002/(SICI)1096-8628(19960122)61:3<277::AID-AJMG14>3.0.CO;2-Q.
The D4Valine194Glycine receptor is a variant of the dopamine D4 receptor and is found in 12.5% of the Afro-Caribbean population. Glycine replaces valine at a position one amino acid away from a serine which is critical for the attachment of dopamine. To determine whether this mutation had an effect on the properties of the dopamine D4 receptor, we constructed this variant and tested the sensitivity of the expressed protein with various drugs. We found that the variant receptor was two orders of magnitude less sensitive to dopamine, clozapine and olanzapine. The variant receptor was insensitive to guanine nucleotide, indicating the absence of a high-affinity state or functional state. The one 15-year-old individual found homozygous for this variant also had sickle cell disease. The patient revealed an overall pattern of low weight and no axillary or pubic hair.
