Page 116 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Chapter 4
Homozygous for a variant
with reduced functionality and heterozygous for a variant with inactive functionality (c.2846A>Tc.2846A>T/*2A+ c.2846A>Tc.2846A>T or c.2846A>Tc.2846A>T/*13+ c.2846A>Tc.2846A>T or c.1236G>A/*2A+c.1236G>A or c.1236G>A/*13+ c.1236G>A)
Heterozygous for a variant with reduced functionality and homozygous for a variant with inactive functionality 2A/*2A+c.2846A>Tc.2846A>T or *2A/*2A+c.1236G>A or *13/*13+ c.2846A>T/c.2846A>T or *13/*13+c.1236G>A)
Homozygous for a variant with inactive functionality
and heterozygous for the other variant with inactive functionality (*2A/*2A+*13 or *13/*2A+*13)
Homozygous for two different variants with reduced functionality (c.2846A>T+c.1236G>A/ c.2846A>T+c.1236G>A)
Homozygous for a variant with reduced functionality and a variant with
inactive functionality +c.2846A>T/*2A+c.2846A>T or *13+c.2846A>T/*13+ c.2846A>T or *2A+c.1236G>A/*2A+ c.1236G>A or *13+c.1236G>A/*13+ c.1236G>A)
Gene activity score 0.5
Gene activity score 0
Gene activity score 0
Gene activity score 0 to 1
(0% to 50% of normal DPD enzyme activity), phenotyping is required to quantify DPD enzyme activity
Gene activity score 0
One of the alleles has an activity of 0.5, the activity of the other allele is 0. Therefore the gene activity score is 0.5.
Both alleles have an activity of 0. Therefore the gene activity score is 0.
Both alleles have an activity of 0. Therefore the gene activity score is 0.
The activity of both alleles is unknown, but lies between 0 and 0.5 (see reasoning for heterozygous for two different reduced functionality alleles).
One should resort to the recommendation for gene activity score 0 when the measured DPD enzyme activity is approximately 0% of normal DPD enzyme activity and the recommendation of gene activity score 1 when the DPD enzyme activity is 50% of normal DPD enzyme activity.
When the measured DPD enzyme activity is between 0% and 50% (e.g. 25%) one should resort to the recommendation for gene activity score 0.5.
Both alleles have an activity of 0. Therefore the gene activity score is 0.
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