title: In vivo characterization of CYP2D6*12, *29 and *84 using dextromethorphan as a probe drug: a case report.
abstract: 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.
authors.affiliation: Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, MO 64108, USA.|School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gaedigk
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Kansas City, Kansas City, MO 64108, USA.
authors.forename: Greyson P
authors.initials: GP
authors.lastname: Twist
authors.affiliation: School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.|Center for Pediatric Genomic Medicine, Children's Mercy Kansas City, Kansas City, MO 64108, USA.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Farrow
authors.affiliation: Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, MO 64108, USA.|School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lowry
authors.affiliation: School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.|Center for Pediatric Genomic Medicine, Children's Mercy Kansas City, Kansas City, MO 64108, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Soden
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Kansas City, Kansas City, MO 64108, USA.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Miller
mesh_terms: D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000652:urine*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000652:urine*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male
chemical_list: D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2D6; CYP2D6*12; CYP2D6*84; dextromethorphan; phenotyping