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dc.contributor.authorIqbal, Zafar
dc.contributor.authorCejudo-Martin, Pilar
dc.contributor.authorde Brouwer, Arjan
dc.contributor.authorvan der Zwaag, Bert
dc.contributor.authorRuiz-Lozano, Pilar
dc.contributor.authorScimia, M. Cecilia
dc.contributor.authorLindsey, James D.
dc.contributor.authorWeinreb, Robert
dc.contributor.authorAlbrecht, Beate
dc.contributor.authorMegarbane, Andre
dc.contributor.authorAlanay, Yasemin
dc.contributor.authorBen-Neriah, Ziva
dc.contributor.authorAmenduni, Mariangela
dc.contributor.authorArtuso, Rosangela
dc.contributor.authorVeltman, Joris A.
dc.contributor.authorvan Beusekom, Ellen
dc.contributor.authorOudakker, Astrid
dc.contributor.authorMillan, Jose Luis
dc.contributor.authorHennekam, Raoul
dc.contributor.authorHamel, Ben
dc.contributor.authorCourtneidge, Sara A.
dc.contributor.authorvan Bokhoven, Hans
dc.date.accessioned2019-12-10T10:36:08Z
dc.date.available2019-12-10T10:36:08Z
dc.date.issued2010
dc.identifier.issn0002-9297
dc.identifier.urihttps://doi.org/10.1016/j.ajhg.2010.01.009
dc.identifier.urihttp://hdl.handle.net/11655/13923
dc.description.abstractFrank-Ter Haar syndrome (FTHS), also known as Ter Haar syndrome, is an autosomal-recessive disorder characterized by skeletal, cardiovascular, and eye abnormalities, such as increased intraocular pressure, prominent eyes, and hypertelorism. We have conducted homozygosity mapping on patients representing 12 FTHS families. A locus on chromosome 5q35.1 was identified for which patients from nine families shared homozygosity. For one family, a homozygous deletion mapped exactly to the smallest region of overlapping homozygosity, which contains a single gene, SH3PXD2B. This gene encodes the TKS4 protein, a phox homology (PX) and Src homology 3 (SH3) domain-containing adaptor protein and Src substrate. This protein was recently shown to be involved in the formation of actin-rich membrane protrusions called podosomes or invadopodia, which coordinate pericellular proteolysis with cell migration. Mice lacking Tks4 also showed pronounced skeletal, eye, and cardiac abnormalities and phenocopied the majority of the defects associated with FTHS. These findings establish a role for TKS4 in FTHS and embryonic development. Mutation analysis revealed five different homozygous mutations in SH3PXD2B in seven FTHS families. No SH3PXD2B mutations were detected in six other FTHS families, demonstrating the genetic heterogeneity of this condition. Interestingly however, dermal fibroblasts from one of the individuals without all SH3PXD2B mutation nevertheless expressed lower levels of the TKS4 protein, Suggesting a common mechanism underlying disease causation.
dc.language.isoen
dc.publisherCell Press
dc.relation.isversionof10.1016/j.ajhg.2010.01.009
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGenetics & Heredity
dc.titleDisruption of the Podosome Adaptor Protein Tks4 (Sh3Pxd2B) Causes The Skeletal Dysplasia, Eye, and Cardiac Abnormalities of Frank-Ter Haar Syndrome
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalAmerican Journal Of Human Genetics
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları
dc.identifier.volume86
dc.identifier.issue2
dc.identifier.startpage254
dc.identifier.endpage261
dc.description.indexWoS
dc.description.indexScopus


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