Subject(s)
Acyltransferases/genetics , Focal Dermal Hypoplasia/genetics , Gene Deletion , Membrane Proteins/genetics , Mosaicism , Mutation , Skin/pathology , Adolescent , DNA Mutational Analysis , Female , Focal Dermal Hypoplasia/enzymology , Focal Dermal Hypoplasia/pathology , Genetic Markers , Genetic Predisposition to Disease , Humans , Phenotype , Young AdultABSTRACT
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.
Subject(s)
Focal Dermal Hypoplasia/genetics , Focal Dermal Hypoplasia/metabolism , Membrane Proteins/deficiency , Signal Transduction/genetics , Wnt Proteins/metabolism , Acyltransferases , Adolescent , Adult , Child , Female , Focal Dermal Hypoplasia/enzymology , Humans , Male , Membrane Proteins/genetics , Middle Aged , Pedigree , Wnt Proteins/physiologyABSTRACT
We describe a fetus with epidermolysis bullosa dystrophica and a fetus with aplasia cutis congenita who were normal by careful ultrasound examination but whose midtrimester amniotic fluids exhibited elevated concentrations of alpha-fetoprotein and presence of acetylcholinesterase. These cases show that serious fetal skin pathology can be a source of amniotic fluid acetylcholinesterase and elevated alpha-fetoprotein concentration and should be considered as part of the differential diagnosis of these amniotic fluid findings.