title: Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia.
abstract: Focal dermal hypoplasia (FDH) is an X-linked dominant multisystem birth defect affecting tissues of ectodermal and mesodermal origin. Using a stepwise approach of (i) genetic mapping of FDH, (ii) high-resolution comparative genome hybridization to seek deletions in candidate chromosome areas and (iii) point mutation analysis in candidate genes, we identified PORCN, encoding a putative O-acyltransferase and potentially crucial for cellular export of Wnt signaling proteins, as the gene mutated in FDH. The findings implicate FDH as a developmental disorder caused by a deficiency in PORCN.
authors.affiliation: Department of Human Genetics, University of Marburg, Bahnhofstr. 7, 35033 Marburg, Germany. grzeschi@staff.uni-marburg.de
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Grzeschik
authors.forename: Dorothea
authors.initials: D
authors.lastname: Bornholdt
authors.forename: Frank
authors.initials: F
authors.lastname: Oeffner
authors.forename: Arne
authors.initials: A
authors.lastname: König
authors.forename: María
authors.initials: M
authors.lastname: del Carmen Boente
authors.forename: Herbert
authors.initials: H
authors.lastname: Enders
authors.forename: Barbara
authors.initials: B
authors.lastname: Fritz
authors.forename: Michael
authors.initials: M
authors.lastname: Hertl
authors.forename: Ute
authors.initials: U
authors.lastname: Grasshoff
authors.forename: Katja
authors.initials: K
authors.lastname: Höfling
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Oji
authors.forename: Mauro
authors.initials: M
authors.lastname: Paradisi
authors.forename: Christian
authors.initials: C
authors.lastname: Schuchardt
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Szalai
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tadini
authors.forename: Heiko
authors.initials: H
authors.lastname: Traupe
authors.forename: Rudolf
authors.initials: R
authors.lastname: Happle
mesh_terms: D000217:Acyltransferases; D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005489:Focal Dermal Hypoplasia / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D015398:Signal Transduction / Q000235:genetics*; D051153:Wnt Proteins / Q000378:metabolism* / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D051153:Wnt Proteins; D000217:Acyltransferases; C491188:PORCN protein, human