title: Mutations in the human SC4MOL gene  encoding a methyl sterol oxidase cause  psoriasiform dermatitis, microcephaly,  and developmental delay.
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.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Kratz
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Michel
authors.forename: Abbe N
authors.initials: AN
authors.lastname: Vallejo
authors.forename: Laura
authors.initials: L
authors.lastname: Ferris
authors.forename: Richard I
authors.initials: RI
authors.lastname: Kelley
authors.forename: Jacqueline J
authors.initials: JJ
authors.lastname: Hoover
authors.forename: Drazen
authors.initials: D
authors.lastname: Jukic
authors.forename: K Michael
authors.initials: KM
authors.lastname: Gibson
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Wolfe
authors.forename: Dhanya
authors.initials: D
authors.lastname: Ramachandran
authors.forename: Michael E
authors.initials: ME
authors.lastname: Zwick
authors.forename: Jerry
authors.initials: J
authors.lastname: Vockley
mesh_terms: D000293:Adolescent; D002784:Cholesterol / Q000378:metabolism; D003872:Dermatitis / Q000235:genetics*; D003873:Dermatitis, Exfoliative / Q000175:diagnosis / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D008540:Meiosis; D008831:Microcephaly / Q000235:genetics*; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics*
chemical_list: D008024:Ligands; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D002784:Cholesterol; D006899:Mixed Function Oxygenases; C027532:methylsterol monooxygenase