Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay.
J Clin Invest
; 121(3): 976-84, 2011 Mar.
Article
in En
| MEDLINE
| ID: mdl-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 oxidaselike 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 ß(LXRα and LXRß), 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Psoriasis
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Developmental Disabilities
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Dermatitis
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Mixed Function Oxygenases
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Microcephaly
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Mutation
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adolescent
/
Female
/
Humans
Language:
En
Journal:
J Clin Invest
Year:
2011
Document type:
Article
Affiliation country:
United States