title: The role of the abnormalities in the distal pathway of cholesterol biosynthesis in the Conradi-Hünermann-Happle syndrome.
abstract: Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata (CP) caused by mutations in one gene of the distal pathway of cholesterol biosynthesis. It exhibits intense phenotypic variation and primarily affects the skin, bones and eyes. The ichthyosis following Blaschko's lines, chondrodysplasia punctata and cataracts are the typical clinical findings. The cardinal biochemical features are an increase in 8(9)-cholestenol and 8-dehydrocholesterol (8DHC), which suggest a deficiency in 3β-hydroxysteroid-Δ8,Δ7-isomerase, also called emopamil binding protein (EBP). The EBP gene is located on the short arm of the X chromosome (Xp11.22-p11.23) and encodes a 230 amino acid protein with dual function. Explaining the clinical phenotype in CDPX2 implies an understanding of both the genetics and biochemical features of this disease. CDPX2 displays an X-linked dominant pattern of inheritance, which is responsible for the distribution of lesions in some tissues. The clinical phenotype in CDPX2 results directly from impairment in cholesterol biosynthesis, and indirectly from abnormalities in the hedgehog signaling protein pathways. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
authors.affiliation: Department of Dermatology, University Hospital of Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain; IBSAL (Instituto de Investigación Biosanitaria de Salamanca), Spain. Electronic address: jcanueto@yahoo.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Cañueto
authors.affiliation: Seccio Errors Congenits del Metabolisme, Servei de Bioquímica Clínica i Genética Molecular, Hospital Clinic Barcelona, Barcelona, Spain.
authors.forename: Marisa
authors.initials: M
authors.lastname: Girós
authors.affiliation: IBSAL (Instituto de Investigación Biosanitaria de Salamanca), Spain; Molecular Medicine Unit, Faculty of Medicine, University of Salamanca, Campus Miguel de Unamuno S/N, Salamanca 37007, Spain; Laboratory 14, IBMCC-CSIC, University of Salamanca, Campus Miguel de Unamuno S/N, Salamanca 37007, Spain.
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
mesh_terms: D002775:Cholestadienols / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000235:genetics; D002806:Chondrodysplasia Punctata / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics; D013251:Steroid Isomerases / Q000235:genetics / Q000378:metabolism
chemical_list: D002775:Cholestadienols; D053823:Hedgehog Proteins; C026359:cholesta-5,8-dien-3 beta-ol; D002784:Cholesterol; D013251:Steroid Isomerases; C022669:delta(8)-delta(7)-sterol isomerase; C090445:EBP protein, human
keywords: CDPX2; Cholesterol; Conradi–Hünermann–Happle syndrome; EBP; Sterol isomerase; X-linked dominant chondrodysplasia punctata