title: Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G-->C genotype.
abstract: Smith-Lemli-Opitz syndrome (RHS) (SLOS, OMIM 270400) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations of the 3beta-hydroxysterol Delta(7)-Delta(8)-reductase gene, DHCR7. We report a fetus with holoprosencephaly and multiple congenital anomalies who was homozygous for the IVS8-1G-->C mutation. Following termination of pregnancy, both the elevated amniotic fluid 7-dehydrocholesterol level and the DHCR7 mutations were demonstrated. Two other newborn infants with IVS8-1G-->C/IVS8-1G-->C genotype are described. This report illustrates a severe phenotypic extreme of SLOS associated with a null genotype, underscores the complex relationship between SLOS and holoprosencephaly, and discusses the possible pathogenetic mechanisms of the development of holoprosencephaly in SLOS.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Canada. nowaczyk@hhsc.ca
authors.forename: M J
authors.initials: MJ
authors.lastname: Nowaczyk
authors.forename: S A
authors.initials: SA
authors.lastname: Farrell
authors.forename: W L
authors.initials: WL
authors.lastname: Sirkin
authors.forename: L
authors.initials: L
authors.lastname: Velsher
authors.forename: P A
authors.initials: PA
authors.lastname: Krakowiak
authors.forename: J S
authors.initials: JS
authors.lastname: Waye
authors.forename: F D
authors.initials: FD
authors.lastname: Porter
mesh_terms: D001483:Base Sequence; D017809:Fatal Outcome; D005313:Fetal Death; D005333:Fetus; D005838:Genotype; D016142:Holoprosencephaly / Q000473:pathology; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010088:Oxidoreductases / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors; D017354:Point Mutation; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics* / Q000473:pathology
chemical_list: D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase