CYP2D6*84 was first described in a Black South African subject, however, its function remains unknown. Astrolabe, a probabilistic scoring tool developed in our laboratory to call genotypes from whole genome sequence, identified CYP2D6*84 in a trio. The father presented with intermediate metabolism when challenged with the CYP2D6 probe drug dextromethorphan (DM/dextrorphan [DX] = 0.0839). Since his second allele, CYP2D6*12, is nonfunctional, the observed activity is derived by CYP2D6*84. This finding suggests that the allele's hallmark P267H causes decreased activity toward DM and that this allele should receive a value of 0.5 for Activity Score calculations. The mother's DM/DX of 0.0543 was consistent with the decreased activity classification of CYP2D6*29. The child, a critically ill neonate, was not phenotyped, but predicted to be a normal metabolizer.
Alleles; Cytochrome P-450 CYP2D6; Dextromethorphan; Female; Humans; Infant, Newborn; Male
CYP2D6; CYP2D6*12; CYP2D6*84; dextromethorphan; phenotyping
Gaedigk, A., Twist, G. P., Farrow, E. G., Lowry, J. A., Soden, S. E., Miller, N. A. In vivo characterization of CYP2D6*12, *29 and *84 using dextromethorphan as a probe drug: a case report. Pharmacogenomics 18, 427-431 (2017).