Distribution of CFTR mutations in the Czech population: Positive impact of integrated clinical and laboratory expertise, detection of novel/de novo alleles and relevance for related/derived populations

AbstractBackgroundThis two decade long study presents a comprehensive overview of the CFTR mutation distribution in a representative cohort of 600 Czech CF patients derived from all regions of the Czech Republic.MethodsWe examined the most common CF-causing mutations using the Elucigene CF-EU2v1™ assay, followed by MLPA, mutation scanning and/or sequencing of the entire CFTR coding region and splice site junctions.ResultsWe identified 99.5% of all mutations (1194/1200 CFTR alleles) in the Czech CF population. Altogether 91 different CFTR mutations, of which 20 were novel, were detected. One case of de novo mutation and a novel polymorphism was revealed.ConclusionThe commercial assay achieved 90.7%, the MLPA added 1.0% and sequencing increased the detection rate by 7.8%. These comprehensive data provide a basis for the improvement of CF DNA diagnostics and/or newborn screening in our country. In addition, they are relevant to related Central European populations with lower mutation detection rates, as well as to the sizeable North American “Bohemian diaspora”

Genetic Modifiers of Liver Disease in Cystic Fibrosis

Context A subset (approximate to 3%-5%) of patients with cystic fibrosis (CF) develops severe liver disease with portal hypertension