Tuberous sclerosis (TSC) is a frequent autosomal-dominant condition (affecting 1 
in 6000 individuals) caused by various mutations in either the hamartin (TSC1) 
or the tuberin gene (TSC2). This allelic and non-allelic heterogeneity makes 
genetic counseling and prenatal diagnosis difficult, especially as a significant 
proportion of TSC cases are due to de novo mutations. For this reason the 
identification of the disease causing mutation is mandatory for accurate 
counseling, yet current mutation detection methods such as single-strand 
conformation polymorphism (SSCP) or denaturing gradient gel electrophoresis 
(DGGE) are labor intensive with limited detection efficiency. Denaturing 
high-performance liquid chromatography (DHPLC) is a high-throughput, 
semi-automated mutation detection system with a reported mutation detection rate 
close to 100% for PCR fragments of up to 800 bp. We used a recently described 
DHPLC assay allowing the efficient detection of mutations in TSC1 to analyze the 
DNA extracted from a chorion villus sample in order to perform a prenatal 
diagnosis for TSC. The fetus was found not to have inherited the deleterious 
mutation and the DHPLC diagnosis was confirmed by haplotype analysis. This 
represents the first DHPLC-based prenatal diagnosis of a genetic disease.