title: Denaturing high-performance liquid chromatography (DHPLC)-based prenatal diagnosis for tuberous sclerosis.
abstract: 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.
authors: Unité de génétique and U-393, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France.
authors: P
authors: P
authors: Bénit
authors: J P
authors: JP
authors: Bonnefont
authors: A
authors: A
authors: Kara Mostefa
authors: C
authors: C
authors: Francannet
authors: A
authors: A
authors: Munnich
authors: P F
authors: PF
authors: Ray
mesh_terms: D002824:Chorionic Villi / Q000737:chemistry; D015193:Chorionic Villi Sampling; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis; D008040:Genetic Linkage; D005865:Gestational Age; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D009691:Nucleic Acid Denaturation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D014402:Tuberous Sclerosis / Q000175:diagnosis* / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins