Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia.
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.
Grzeschik
Karl-Heinz
KH
Department of Human Genetics, University of Marburg, Bahnhofstr. 7, 35033 Marburg, Germany. grzeschi@staff.uni-marburg.de
Bornholdt
Dorothea
D
Oeffner
Frank
F
König
Arne
A
del Carmen Boente
María
M
Enders
Herbert
H
Fritz
Barbara
B
Hertl
Michael
M
Grasshoff
Ute
U
Höfling
Katja
K
Oji
Vinzenz
V
Paradisi
Mauro
M
Schuchardt
Christian
C
Szalai
Zsuzsanna
Z
Tadini
Gianluca
G
Traupe
Heiko
H
Happle
Rudolf
R
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
D008565:Membrane Proteins; D051153:Wnt Proteins; D000217:Acyltransferases; C491188:PORCN protein, human