| Discordant phenotype and sterol biochemistry in Smith-Lemli-Opitz syndrome. | |
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MedLine Citation:
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PMID: 20635399 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome resulting from mutations of the 7-dehydrocholesterol reductase (DHCR7) gene. During cholesterol biosynthesis, DHCR7 catalyzes the conversion of 7-dehydrocholesterol (7DHC) to cholesterol. A clinical diagnosis of SLOS is confirmed biochemically by the presence of elevated levels of 7DHC. Phenotypic severity of SLOS has previously been shown to correlate with the 7DHC/cholesterol ratio. We describe a patient with a severe SLOS phenotype, but a very low serum 7DHC/cholesterol ratio. We show that this discordance is due to alternative splicing of a previously unreported IVS5+3 A>T mutation. This mutation results in the transcription of both normal and mutant mRNA transcripts. We postulate that alternative splicing of the IVS5+3 A>T results in insufficient DHCR7 activity during embryogenesis, but sufficient DHCR7 activity once cholesterol synthetic rates decrease postnatally. This unique case underscores the adjunctive use of fibroblast and molecular testing in ambiguous cases of SLOS and may provide insight into the potential efficacy of therapeutic interventions altering postnatal cholesterol biosynthesis. |
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Authors:
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Grace Koo; Sandra K Conley; Christopher A Wassif; Forbes D Porter |
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Publication Detail:
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Type: Case Reports; Journal Article; Research Support, N.I.H., Intramural |
Journal Detail:
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Title: American journal of medical genetics. Part A Volume: 152A ISSN: 1552-4833 ISO Abbreviation: Am. J. Med. Genet. A Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-11-15 Revised Date: 2011-07-20 |
Medline Journal Info:
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Nlm Unique ID: 101235741 Medline TA: Am J Med Genet A Country: United States |
Other Details:
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Languages: eng Pagination: 2094-8 Citation Subset: IM |
Affiliation:
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Section on Molecular Dysmorphology, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, DHHS, Bethesda, MD, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Cholesterol / metabolism Dehydrocholesterols / metabolism Female Humans Infant, Newborn Male Mutation / genetics* Oxidoreductases Acting on CH-CH Group Donors / genetics* Phenotype Smith-Lemli-Opitz Syndrome / diagnosis, genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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ZIA HD008825-03/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dehydrocholesterols; 434-16-2/7-dehydrocholesterol; 57-88-5/Cholesterol; EC 1.3.-/Oxidoreductases Acting on CH-CH Group Donors; EC 1.3.1.21/7-dehydrocholesterol reductase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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