title: Mutations in the Delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome.
abstract: The Smith-Lemli-Opitz syndrome (SLOS) is an inborn disorder of sterol metabolism with characteristic congenital malformations and dysmorphias. All patients suffer from mental retardation. Here we identify the SLOS gene as a Delta7-sterol reductase (DHCR7, EC 1.3.1. 21) required for the de novo biosynthesis of cholesterol. The human and murine genes were characterized and assigned to syntenic regions on chromosomes 11q13 and 7F5 by fluorescense in situ hybridization. Among the mutations found in patients with the SLOS, are missense (P51S, T93M, L99P, L157P, A247V, V326L, R352W, C380S, R404C, and G410S), nonsense (W151X), and splice site (IVS8-1G>C) mutations as well as an out of frame deletion (720-735 del). The missense mutations L99P, V326L, R352W, R404C, and G410S reduced heterologous protein expression by >90%. Our results strongly suggest that defects in the DHCR7 gene cause the SLOS.
authors.affiliation: Institut für Biochemische Pharmakologie, Universität Innsbruck, Peter Mayr Strasse 1, A-6020 Innsbruck, Austria.
authors.forename: B U
authors.initials: BU
authors.lastname: Fitzky
authors.forename: M
authors.initials: M
authors.lastname: Witsch-Baumgartner
authors.forename: M
authors.initials: M
authors.lastname: Erdel
authors.forename: J N
authors.initials: JN
authors.lastname: Lee
authors.forename: Y K
authors.initials: YK
authors.lastname: Paik
authors.forename: H
authors.initials: H
authors.lastname: Glossmann
authors.forename: G
authors.initials: G
authors.lastname: Utermann
authors.forename: F F
authors.initials: FF
authors.lastname: Moebius
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D016415:Sequence Alignment; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics*
chemical_list: C033144:lathosterol delta-5-dehydrogenase; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors