APPLICATION OF MOLECULAR-GENETICS IN PUBLIC-HEALTH - IMPROVED FOLLOW-UP IN A NEONATAL HEMOGLOBINOPATHY SCREENING-PROGRAM

Newborn screening for the hemoglobinopathies has been shown to reduce morbidity and mortality, particularly for sickle cell anemia, by facil itating initiation of penicillin prophylaxis by 4 months of age. The p urpose of the current investigation was to determine whether molecular genetic follow-up testing could be introduced into a neonatal hemoglo binopathy screening program and, if successfully introduced, whether i t would reduce time to diagnostic confirmation. Between July 1, 1991, and October 7, 1992, 518 original dried blood specimens were referred from the Texas Department of Health Neonatal Hemoglobinopathy Screenin g Program for molecular genetic follow-up testing. Allele-specific cle avage (ASC) after amplification with matched and mismatched polymerase chain reaction primers was compared to allele-specific oligonucleotid e (ASO) hybridization. By November 2, 1992, molecular genetic analyses were definitive in 506, and agreement was observed between ASC and AS O hybridization in all specimens analyzed. Approximately 13% of those initially screened FS were considered probable S/beta-thal by DNA and RNA testing. Rapid molecular genetic analysis contributed to a substan tial reduction of the mean age at confirmation by approximately 50%, t o about 2 months of age. ASC is a reliable method for molecular geneti c analysis of dried blood specimens, providing methodology which can b e readily automated. An automated method is demonstrated that is based on microtiter plate technology and will significantly reduce labor in tensity and costs, while increasing sample throughput. Even with curre nt manual testing methods, DNA and RNA analysis of initial newborn scr eening specimens will reduce the age at confirmation well under 4 mont hs, the age cut-off for effective initiation of penicillin prophylaxis . (C) 1994 Academic Press, Inc.