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.
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ABSTRACT: Signaling pathways are an ever present force in every ani- mal's life. During development, these pathways provide critical cell-cell communication required to coordinate the activities of vast numbers of cells. In adulthood, similar communication mechanisms are utilized to achieve tissue homeostasis and regeneration. Regulation of signaling is crucial; too much or too little activity from a given signal transduction pathway can cause devastating results such as developmental defects or, later in life, disease. The Wnts comprise a large family of highly conserved growth factors that are responsible for important developmental and homeostatic processes throughout the animal kingdom (for a more comprehensive review see Ref. 1). Their implication in a wide array of developmental events and human diseases has made Wnts and their signaling pathways the subject of intense investi- gation over the last two decades. This has never been truer than in the past few years, when the association of Wnt signaling with stem cell fate has added fuel to an already active field. Membership in the Wnt family is defined by amino acid sequence rather than functional properties. It is therefore not too surprising that Wnts have been associated with a number of different activities and downstream signaling pathways. Although the majority of work in the field to date has focused on -catenin-dependent, or canonical, Wnt signaling, exam- ples continue to accumulate in which Wnts and/or other key components of the canonical signaling cascade participate in -catenin-independent processes (reviewed in Ref. 2). In this review, we will focus largely on the canonical pathway, paying particular attention to recent insights. We will then touch on some developments in -catenin-independent signaling and discuss some issues that may be important to all Wnts, regard- less of the signal they generate.Journal of Biological Chemistry 09/2006; 281(32):22429-33. · 4.65 Impact Factor
Article: A WNTer wonderland in Snowbird.[show abstract] [hide abstract]
ABSTRACT: The Keystone Symposium on ;Wnt and beta-catenin signaling in development and disease' was held recently in Snowbird, UT, USA. Organized by Mariann Bienz and Hans Clevers, this meeting covered a wide range of topics, including Wnt protein biogenesis, Wnt receptors and signaling pathways, beta-catenin/Tcf complexes and gene expression, Wnt signaling in development, cancer, stem cell biology and regeneration, and therapeutics that target the Wnt/beta-catenin pathway.Development 08/2006; 133(14):2597-603. · 6.21 Impact Factor
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ABSTRACT: We describe a girl who was diagnosed with split foot-split hand anomaly prenatally, in whom at birth the diagnosis of Van Allen-Myhre syndrome was made, and who at 8 months of age was recognized to have Goltz syndrome. Based on the evolution of clinical features in this infant, we suggest that our case, as well as that reported by Van Allen and Myhre, is an example of unusually severe Goltz syndrome.American Journal of Medical Genetics 08/2002; 110(4):370-9.