|Van Den Veyver, Ignatia|
Submitted to: Nature Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/30/2007
Publication Date: 7/1/2007
Citation: Wang, X., Sutton, V.R., Peraza-Llanes, J.O., Yu, Z., Rosetta, R., Kou, Y., Eble, T.N., Patel, A., Thaller, C., Fang, P., Van den Veyver, I.B. 2007. Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia. Nature Genetics. 39(7):836-838.
Interpretive Summary: In addition to studying the role of prenatal nutrition, we are interested in human developmental disorders that have a prenatal onset. This work deals with a rare condition, Goltz Syndrome that is associated with multiple defects of various organs and structures. We hypothesized that the gene for this disorder should have a very important function in normal human development. We believe that understanding key players in critical developmental pathways via gene identification for seemingly rare disorders contributes significantly to the understanding of human development in general and how such pathways could be influenced by prenatal environmental factors, including nutrition. We found that Goltz Syndrome is caused by mutations in the PORCN gene. This gene is very important because it regulates one of the most important developmental pathways in most organisms, Wnt (Wingless-type MMTV integration site family) signaling, which orchestrates the development and patterning of most organs in the body. Wnt signaling is susceptible to environmental influences, perhaps also nutrition. While not immediately resulting from the USDA research project, these studies significantly increase our expertise in developmental biology research and may have a long-term contribution to the nutritional influences on development.
Technical Abstract: Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular, and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and found heterozygous and mosaic mutations in PORCN in other affected females and males, respectively. PORCN encodes the human homolog of Drosophila melanogaster porcupine, an endoplasmic reticulum protein involved in secretion of Wnt proteins.