Journal article
Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay
The Journal of clinical investigation, Vol.121(3), pp.976-984
03/01/2011
Handle:
https://hdl.handle.net/2376/110437
PMCID: PMC3049385
PMID: 21285510
Abstract
Defects in cholesterol synthesis result in a wide variety of symptoms, from neonatal lethality to the relatively mild dysmorphic features and developmental delay found in individuals with Smith-Lemli-Opitz syndrome. We report here the identification of mutations in sterol-C4-methyl oxidase–like gene (
SC4MOL
) as the cause of an autosomal recessive syndrome in a human patient with psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay. This gene encodes a sterol-C4-methyl oxidase (SMO), which catalyzes demethylation of C4-methylsterols in the cholesterol synthesis pathway. C4-Methylsterols are meiosis-activating sterols (MASs). They exist at high concentrations in the testis and ovary and play roles in meiosis activation. In this study, we found that an accumulation of MASs in the patient led to cell overproliferation in both skin and blood. SMO deficiency also substantially altered immunocyte phenotype and in vitro function. MASs serve as ligands for liver X receptors α and β (LXRα and LXRβ), which are important in regulating not only lipid transport in the epidermis, but also innate and adaptive immunity. Deficiency of SMO represents a biochemical defect in the cholesterol synthesis pathway, the clinical spectrum of which remains to be defined.
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Details
- Title
- Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay
- Creators
- Miao He - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USALisa E Kratz - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USAJoshua J Michel - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USAAbbe N Vallejo - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USALaura Ferris - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USARichard I Kelley - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USAJacqueline J Hoover - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USADrazen Jukic - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USAK. Michael Gibson - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USALynne A Wolfe - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USADhanya Ramachandran - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USAMichael E Zwick - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USAJerry Vockley - Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA
- Publication Details
- The Journal of clinical investigation, Vol.121(3), pp.976-984
- Academic Unit
- Pharmacotherapy, Department of
- Publisher
- American Society for Clinical Investigation
- Identifiers
- 99900547646401842
- Language
- English
- Resource Type
- Journal article