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 defects such as phenylketonuria, galactosemia, hypothyroidism and hemoglobinopathies. The advent of molecular techniques, specifically polymerase chain reaction (PCR), has resulted in unparalleled advances in diagnostic sensitivity. Because of its ability to amplify small quantities of deoxyribonucleic acid (DNA), PCR has proven particularly successful for use with Guthrie card bloodspots in the identification of many genetic disorders including cystic fibrosis, sickle cell anemia and muscular dystrophy. Furthermore, it has been suggested that Guthrie cards represent a vast archive of genomic material yet to be explored. In this article we review our experience using Guthrie card bloodspots for PCR amplification of the cystic fibrosis gene, describe the advantages and limitations of this technology and speculate on future prospects for molecular diagnostics over the next 100 years.