Rapid genetic diagnosis and prenatal diagnosis of spinal muscular atrophy by denaturing high-performance liquid chromatography

摘要

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder (1 in 6000 to 10 000 births) caused by mutations in the SMN1 gene at 5q13. More than 90%-98% of SMA patients show homozygous deletion of SMN1, which has proved to be useful in the diagnosis of SMA. But it is hampered because of the existence of a highly homologous gene, SMN2. Based on nucleotide mismatches between SMN1 and SMN2, the following two DNA tests are usually performed: single-strand conformational polymorphism (SSCP) and polymerase chain reaction (PCR) followed by a restriction enzyme digestion. In this study we developed a new method for rapid genetic diagnosis of SMA by denaturing high-performance liquid chromatography (DHPLC), which is based on different retention of homoduplexes and heteroduplexes in detecting the homozygous deletion of SMN1. Both genetic and prenatal diagnoses were performed successfully for a SMA family by DHPLC, which was confirmed as a rapid and effective technique for detecting the deletion of SMN1.