Page 117 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Homozygous for two different Gene activity score 0 variants with inactive
functionality
(*2A+*13/*2A+ *13)
Patients carrying three or more variants
Both alleles have an activity of 0. Therefore the gene activity score is 0.
Genotype result
Three or more variants
Reasoning for finding the possible predicted phenotype
Since patients carrying three or more different variants are rare, only a general explanation of how to predict the phenotype is given. If one does encounter a 4 patient carrying three or more variants, one must determine how these variants
can be located among two alleles and determine if this leads to different
predicted phenotypes.
Since there are only two validated variants which result in a reduced functionality, an allele with three different variants will always have a variant with an inactive functionality and therefore the allele will have an activity of 0. The predicted allele activities for alleles with 0, 1 or 2 variants are indicated in the tables above.
If all possible distributions of the variants across the alleles lead to the same gene activity score of the genotype (i.e. the sum of allele activities), then one can conclude this as the patient’s gene activity score.
If different distributions lead to genotypes with different gene activity scores, phenotyping is required to quantify DPD enzyme activity.
Supplement
Abbreviation: DPD: dihydropyrimidine dehydrogenase.
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