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Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay
Miao He, … , Michael E. Zwick, Jerry Vockley
Miao He, … , Michael E. Zwick, Jerry Vockley
Published February 1, 2011
Citation Information: J Clin Invest. 2011;121(3):976-984. https://doi.org/10.1172/JCI42650.
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Research Article Development

Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay

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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.

Authors

Miao He, Lisa E. Kratz, Joshua J. Michel, Abbe N. Vallejo, Laura Ferris, Richard I. Kelley, Jacqueline J. Hoover, Drazen Jukic, K. Michael Gibson, Lynne A. Wolfe, Dhanya Ramachandran, Michael E. Zwick, Jerry Vockley

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Plasma sterol analysis of controls; patient before cholesterol supplemen...

Plasma sterol analysis of controls; patient before cholesterol supplementation; patient after 3 months of cholesterol supplementation; and the patient’s mother and father


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