Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia.

Department of Human Genetics, University of Marburg, Bahnhofstr. 7, 35033 Marburg, Germany.
Nature Genetics (Impact Factor: 29.65). 08/2007; 39(7):833-5. DOI: 10.1038/ng2052
Source: PubMed

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.

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    ABSTRACT: Focal dermal hypoplasia (FDH), Goltz syndrome, or Goltz–Gorlin syndrome (OMIM #305600) is a rare X-linked dominant disease. Mutation in the PORCN gene (Xp11.23) causes defective Wnt signaling and results in widespread dysplasia of ectoderm and mesoderm.[1,2] The most distinctive change is skin atrophy that appears as streaky atrophic plaques, unilateral or bilateral, along the Blaschko’s lines. Atrophic plaques contain dermal fat dysplasia and may develop nodular outpouching. Other classical changes are papillomatous growths around lips, anus, and eyes, patchy alopecia, aplasia cutis, palmoplantar hyperkeratosis and hyperhidrosis, abnormalities in the bones and eyes, presence of hernias, and a typical facial appearance. Herein, we report two cases of focal dermal hypoplasia with large and extreme abdominal wall dehiscence.
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