Mutations in the Δ7-sterol reductase gene in patients with the Smith–Lemli–Opitz syndrome
Open accessAbstract
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.
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Smith-Lemli-Opitz syndrome (SLOS) is caused by deficiency of 7-dehydrocholesterol reductase, the enzyme responsible for the last step of cholesterol biosynthesis, resulting from mutations in DHCR7.
“Smith–Lemli–Opitz syndrome (SLOS) is caused by the deficiency of 7-dehydrocholesterol (7DHC) reductase, the enzyme responsible for the last step of cholesterol biosynthesis [44], resulting from mutations in DHCR7 [45–47].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [45]
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Research works printed but not linked: 2
- [4]Moebius, F. F., Fitzky, B. U., Lee, J. N., Paik, Y.-K. & Glossmann, H. (1998) Proc. Natl. Acad. Sci. USA 95, 1899-1902.
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- Authors
- Fitzky, B. U., Witsch-Baumgartner, M., Erdel, M., Lee, J. N., Paik, Y.-K., Glossmann, H., Utermann, G., & Moebius, F. F.
- Affiliations
- Universität Innsbruck (AT)
- Institut für Biochemische Pharmakologie, Universität Innsbruck, Peter Mayr Strasse 1, A-6020 Innsbruck, Austria; Institut für Medizinische Biologie und Humangenetik, Schöpfstrasse 41, A-6020 Innsbruck, Austria; and Department of Biochemistry and Bioproducts Research Center Yonsei University, Seoul 120–749, Korea
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1998-07-07
- Volume
- 95
- Issue
- 14
- Pages
- 8181-8186
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC20950
- OpenAlex
- W2008679927
- Cited by
- 384
- References
- 0
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 9 · 2023: 4 · 2022: 13 · 2021: 9 · 2020: 14 · 2019: 5 · 2018: 4 · 2017: 5 · 2016: 11 · 2015: 9 · 2014: 16 · 2013: 9 · 2012: 8
- FWCI
- 20.66
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- Smith-Lemli-Opitz syndrome, DHCR7, sterol metabolism, cholesterol biosynthesis, missense mutations, nonsense mutation, splice site mutation, frameshift deletion, chromosome 11q13, congenital malformations, intellectual disability, gene mapping
- MeSH terms
- Amino Acid Sequence, Animals, Chromosome Mapping, Chromosomes, Human, Pair 11, Cloning, Molecular, Female, Humans, Male, Molecular Sequence Data, Mutation, Oxidoreductases, Sequence Alignment, Smith-Lemli-Opitz Syndrome, Oxidoreductases Acting on CH-CH Group Donors, Mice
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