Mutation screening for prenatal and presymptomatic diagnosis: cystic fibrosis and haemochromatosis

Hereditary haemochromatosis (HH) and cystic fibrosis (CF) are the most comm on autosomal recessively inherited disorders in Caucasian populations. In i ts typical form, CF manifests during the first years of life, while the mea n age of onset of organ damage is 54 years in HH. Both disorders can be dia gnosed presymptomatically utilising biochemical and/or genetic testing. Sin ce approximately 90% of mid-European HH patients are homozygous for only on e specific mutation (C282Y) in the candidate gene for HH, genetic testing i s simple and sensitive in HH. In CF. molecular testing is currently hampere d by the large number (more than 800) of mutations in the CF transmembrane conductance regulator gene. Several studies have been initiated to investig ate the potential benefits and the best time and mode of presymptomatic tes ting for HH and CF. Conclusion Mutation analysis is widely recommended for presymptomatic diagn osis of cystic fibrosis and hereditary haemochromatosis because of the pres umed benefit, although several medical, ethical, social and technical quest ions warrant further investigations. Prenatal mutation testing is commonly performed for cystic fibrosis but not for hereditary haemochromatosis. Info rmed consent of tested individuals and the availability of genetic counsell ing is a prerequisite for any mutation screening approach in either disease .