Rapid prenatal diagnosis of spinal muscular atrophy by denaturing high‐performance liquid chromatography system

OBJECTIVE: Use of Denaturing High-Performance Liquid Chromatography (DHPLC) in prenatal diagnosis of spinal muscular atrophy (SMA). METHODS: Thirty-three members of 7 families participated in carrier test and disease detection of SMA. Prenatal genetic diagnosis was performed if both parents were carriers or any family members had SMA. DNA extracted from blood, chorionic villi and amniotic fluid was amplified and used for DHPLC. RESULTS: Twenty SMA carriers, seven SMA affected cases, and six normal individuals were identified. SMA status was demonstrated by genotyping and total copy number determinations of SMN1 and SMN2. Families 1-3 were classified as group one (SMA affecting previously born child). Group two, comprising families 4 and 5, had lost a child due to an unknown muscular disease. Group three (SMA-affected parent) comprised families 6 and 7; carrier testing was done. DHPLC prenatal genetic diagnosis was made in seven pregnancies, one in each family (affected, n=2; carrier, n=3; normal, n=2). Pregnancy was terminated for the two affected fetuses. The others were delivered uneventfully and SMA free. CONCLUSION: DHPLC prenatal diagnosis of SMA and determination of SMA status in adults is possible, and SMN1 and SMN2 copy numbers can be determined.