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Denaturing high‐performance liquid chromatography (DHPLC)‐based prenatal diagnosis for tuberous sclerosis
Author(s) -
Bénit Paule,
Bonnefont JeanPaul,
Kara Mostefa Ali,
Francannet Christine,
Munnich Arnold,
Ray Pierre F.
Publication year - 2001
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.55
Subject(s) - denaturing high performance liquid chromatography , tuberous sclerosis , tsc1 , prenatal diagnosis , mutation , biology , genetics , genetic counseling , microbiology and biotechnology , haplotype , allele , gene , fetus , medicine , pathology , pregnancy , apoptosis , pi3k/akt/mtor pathway
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. Copyright © 2001 John Wiley & Sons, Ltd.