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.