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.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Gaedigk A,Twist GP,Farrow EG,Lowry JA,Soden SE,Miller NA

doi

10.2217/pgs-2016-0192

subject

Has Abstract

pub_date

2017-04-01 00:00:00

pages

427-431

issue

5

eissn

1462-2416

issn

1744-8042

journal_volume

18

pub_type

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