| Autor: |
Kaatje Heinelt, Juliane Strien, Annalisa Patrizi, María del Carmen Boente, Karl-Heinz Grzeschik, Yasemin Alanay, Nicolas Chassaing, Ben C.J. Hamel, Ingo Lohrisch, Marie Eleanore O. Nicolas, G. Eda Utine, Ian O. Ellis, Carlo Marcelis, Jeffrey A. Ascherman, Katrina Prescott, Bart Loeys, Arne König, Mauro Paradisi, Christina Raissa I. Francisco, Wolfgang Kastrup, Frank Oeffner, Patricia Silvia Della Giovanna, Paul J. Benke, Dorothea Bornholdt, Maria Piccione, Yasmin Mehraein, Cristina Has, Andreas R. Janecke, Ineke van der Burgt, Bettina Prager, Dana Pagliarini, Hildegunde Piza-Katzer, Marc S. Zeller, Rudolf Happle |
| Rok vydání: |
2009 |
| Předmět: |
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| Zdroj: |
Human Mutation. 30:E618-E628 |
| ISSN: |
1059-7794 |
| DOI: |
10.1002/humu.20992 |
| Popis: |
The X-linked dominant trait focal dermal hypoplasia (FDH, Goltz syndrome) is a developmental defect with focal distribution of affected tissues due to a block of Wnt signal transmission from cells carrying a detrimental PORCN mutation on an active X-chromosome. Molecular characterization of 24 unrelated patients from different ethnic backgrounds revealed 23 different mutations of the PORCN gene in Xp11.23. Three were microdeletions eliminating PORCN and encompassing neighboring genes such as EBP, the gene associated with Conradi-Hunermann-Happle syndrome (CDPX2). 12/24 patients carried nonsense mutations resulting in loss of function. In one case a canonical splice acceptor site was mutated, and 8 missense mutations exchanged highly conserved amino acids. FDH patients overcome the consequences of potentially lethal X-chromosomal mutations by extreme skewing of X-chromosome inactivation in females, enabling transmission of the trait in families, or by postzygotic mosaicism both in male and female individuals. Molecular characterization of the PORCN mutations in cases diagnosed as Goltz syndrome is particularly relevant for genetic counseling of patients and their families since no functional diagnostic test is available and carriers of the mutation might otherwise be overlooked due to considerable phenotypic variability associated with the mosaic status. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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