CYSTIC-FIBROSIS - MOLECULAR APPROACHES TO DIAGNOSIS

Whole blood collected on filter paper (Guthrie cards) has provided an excellent means for screening inborn errors of metabolism in neonates. Traditional biochemical methods adapted for use with this collection device have proven instrumental in the detection of many congenital de fects such as phenylketonuria, galactosemia, hypothyroidism and hemogl obinopathies. The advent of molecular techniques, specifically polymer ase chain reaction (PCR), has resulted in unparalleled advances in dia gnostic sensitivity. Because of its ability to amplify small quantitie s of deoxyribonucleic acid (DNA), PCR has proven particularly successf ul for use with Guthrie card bloodspots in the identification of many genetic disorders including cystic fibrosis, sickle cell anemia and mu scular dystrophy. Furthermore, it has been suggested that Guthrie card s represent a vast archive of genomic material yet to be explored. In this article we review our experience using Guthrie card bloodspots fo r PCR amplification of the cystic fibrosis gene, describe the advantag es and limitations of this technology and speculate on future prospect s for molecular diagnostics over the next 100 years.