Background Around 20-30% of all prescribed drugs are estimated to be metabolised by the cytochrome P450 (CYP) 2D6 enzyme. In a medical practice, it is usually not known whether a patient is a poor, intermediate, normal or ultra-rapid metaboliser for CYP2D6-metabolised drugs. Objective This study aims to explore the clinical relevance and the extent of hazardous prescriptions by analysing the metaboliser status of patients already taking such drugs. Methods This is a family practice-based observational study performed in a rural practice for general and family medicine in Lower Austria providing care for approximately 2100 patients annually. In 287 consecutive patients, who had taken or were taking a drug metabolised by CYP2D6 during the last 3 years, the metaboliser status was analysed. Results The genetic analysis of 287 patients resulted in 51.22% normal metabolisers, 38.68% intermediate metabolisers, 6.27% poor metabolisers and 3.83% ultra-rapid metabolisers. In 50 cases (poor metaboliser, intermediate metaboliser and ultra-rapid metaboliser, i.e. 17.42% of all tested patients taking a CYP2D6-specific drug), an altered gene function was identified, for which clinical guideline annotations, drug label annotations, or clinical annotations are available. Allele and genotype frequencies were in accordance with data from other European studies. Conclusions In 17.42% of all patients already taking a drug metabolised by CYP2D6, knowledge of the genetically defined metaboliser status would have been of immediate clinical relevance before prescribing the drug. ClinicalTrials.gov identifier NCT03859622.

Adamantinoma is a low-grade, malignant biphasic bone tumour predominantly located in the tibia. In up to 50% of all cases this is combined with one or more lesions in the ipsilateral fibula. Whether these lesions represent regional metastases or arise de novo is not yet exactly known. In order to address this question, we extracted DNA from the respective fresh frozen tumour tissues in a case of a young woman with a multifocal adamantinoma of both the tibia and ipsilateral fibula. Afterwards the X inactivation pattern was studied by means of methylation-sensitive polymerase chain reaction and primers that target the polymorphic CGG trinucleotide repeat of FMR1 gene and the polymorphic CAG repeat, on exon 1 of the human androgen receptor gene (AR). The analysis of the AR was homozygous and not informative. Studying the FMR1 gene, we detected a 100% skewing of the X inactivation pattern of both locations and found that the same allele was methylated. Even if the fibula lesion arose de novo there would have been a 50 : 50 chance that the same allele was methylated. As this methylation pattern was found we cannot provide a valid explanation for the origin of the fibula lesion. Analysis of X inactivation patterns in future cases of polyfocal adamantinoma might provide further evidence for one of the two theories.

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