Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
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.
View: Text | PDF
Research Article Development

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

  • Text
  • PDF
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

×

Figure 1

Severe scaling and psoriasiform dermatitis in the patient.

Options: View larger image (or click on image) Download as PowerPoint
Severe scaling and psoriasiform dermatitis in the patient.
(A) Note mild...
(A) Note mild microcephaly, lusterless, fine fair hair, and blepharitis. (B and C) The ichthyosiform erythroderma covers all of the patient’s body except for the palms and soles. (D) H&E-stained section of affected skin shows hyperkeratosis (original magnification, ×10), loss of granular layer, psoriasiform hyperplasia, thinning of suprapapillary plate, and neutrophilic epidermal infiltration; these features are characteristic of psoriasis. (E) Oil red O staining of affected skin biopsy (original magnification, ×20) The arrow shows the intracellular lipid accumulation in the foamy cells in the dermis. (F) Neutrophil elastase staining (shown in red) of neutrophils in the stratum corneum of affected skin (original magnification, ×20). Photographs reproduced with signed informed consent/assent provided by the patient and her family.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts