Mutations in the Δ7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome

Barbara U. Fitzky, Martina Witsch-Baumgartner, Martin Erdel, Joon No Lee, Young Ki Paik, Hartmut Glossmann, Gerd Utermann, Fabian F. Moebius

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305 Citations (Scopus)

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 Δ7-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.

Original languageEnglish
Pages (from-to)8181-8186
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number14
DOIs
Publication statusPublished - 1998 Jul 7

All Science Journal Classification (ASJC) codes

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