Molecular genetic analysis of cystic fibrosis (CF) is routinely performed in hundreds of laboratories worldwide. The Orphanet database (www.orpha.net) lists 302 CF diagnostic laboratories (44 for Germany). Most laboratories use commercial kits that are expected to be robust and deliver reliable results. For most European populations, CFTR mutation detection rates of 70–90% can be achieved by testing the most frequent mutations (which are mainly included in commercial kits), thereby identifying homozygosity or compound heterozygosity for CFTR mutations in approximately 50–80% of CF patients. Very often, the referring clinicians (mostly paediatricians or geneticists) request testing of only the CF patients and not of their parents. At the Institute of Human Genetics in Hannover, we have tested 2168 patients with the clinical diagnosis of CF, but we have received samples only from the parents (mostly after having tested the index patients) in 198 (9.1%) of these cases. However, as again stated in the best practice guidelines for molecular genetic analysis of CF- and CFTR-related disorders in the European Journal of Human Genetics, ‘identification of mutation(s) on both parental alleles is required to confirm the diagnosis. Homozygous and compound heterozygous status should thus be confirmed by studying the parents’.1 Here, we present two recent cases from our laboratories that strengthen the need to correctly assign the parental alleles, particularly in the context of prenatal diagnosis of CF or carrier testing.
Strategische Forschungsbereiche und Zentren
- Querschnittsbereich: Medizinische Genetik