title: First trimester prenatal diagnosis of Smith-Lemli-Opitz syndrome (7-dehydrocholesterol reductase deficiency).
abstract: In Smith-Lemli-Opitz syndrome (SLOs), 7-dehydrocholesterol (7-DHC) accumulated because there is a block in the pathway for synthesis of cholesterol via 7-DHC. Prenatal diagnosis of SLOs has been achieved by analysis of 7-DHC in amniotic fluid obtained at 16-18 wk from pregnancies at risk. The purpose of this study was to investigate 7-DHC and cholesterol concentrations in chorionic villus (CV) samples with a view to performing first trimester prenatal diagnosis. Using a sensitive gas chromatography-mass spectrometry assay it was possible to detect 7-DHC in CV samples obtained as early as 7 wk of gestation. The ration of 7-DHC to cholesterol in placental tissue was shown to be relatively constant over the gestational period of 7-18 wk. We therefore proceeded to analyze the 7-DHC/cholesterol ration in CV samples taken at 10-12 wk of gestation from three pregnancies at risk for SLOs. The results were as follows: patient A, 1.10 x 10(-3); patient B, 1.80 x 10(-3); patient C, 0.091; control range for CVS (8-12 wk), 3.10 x 10(-4) to 1.62 x 10(-3) (mean +/- 2SD; n = 5). The fetus of patient C was diagnosed as affected by SLOs, and the parents requested termination. Analysis of cultured skin fibroblasts confirmed the diagnosis. Pregnancies A and B were diagnosed unaffected, and this was confirmed first by amniocentesis and then by the birth of normal infants at term. We conclude that synthesis of cholesterol via 7-DHC is occurring in the placenta and/or fetus at 10 wk of gestation and that prenatal diagnosis by CV biopsy is possible.
authors.affiliation: Biochemistry Unit, Institute of Child Health, London, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Mills
authors.forename: H
authors.initials: H
authors.lastname: Mandel
authors.forename: R
authors.initials: R
authors.lastname: Montemagno
authors.forename: P
authors.initials: P
authors.lastname: Soothill
authors.forename: R
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.forename: P T
authors.initials: PT
authors.lastname: Clayton
mesh_terms: D000649:Amniocentesis; D000653:Amniotic Fluid / Q000201:enzymology / Q000378:metabolism; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism; D002824:Chorionic Villi / Q000201:enzymology / Q000378:metabolism; D015193:Chorionic Villi Sampling; D005260:Female; D005865:Gestational Age; D006801:Humans; D010088:Oxidoreductases / Q000172:deficiency*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011247:Pregnancy; D011296:Prenatal Diagnosis; D019082:Smith-Lemli-Opitz Syndrome / Q000175:diagnosis* / Q000201:enzymology* / Q000378:metabolism
chemical_list: D002784:Cholesterol; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase