title: De novo exon 1 missense mutations of SKI and Shprintzen-Goldberg syndrome: two new cases and a clinical review.
abstract: Shprintzen-Goldberg syndrome (OMIM #182212) is a connective tissue disorder characterized by craniosynostosis, distinctive craniofacial features, skeletal abnormalities, marfanoid body habitus, aortic dilatation, and intellectual disability. Mutations in exon 1 of SKI have recently been identified as being responsible for approximately 90% of reported individuals diagnosed clinically with Shprintzen-Goldberg syndrome. SKI is a known regulator of TGFβ signaling. Therefore, like Marfan syndrome and Loeys-Dietz syndrome, Shprintzen-Goldberg syndrome is likely caused by deregulated TGFβ signals, explaining the considerable phenotypic overlap between these three disorders. We describe two additional patients with exon 1 SKI mutations and review the clinical features and literature of Shprintzen-Goldberg syndrome.
authors.affiliation: Department of Medical Genetics, Alberta Children's Hospital, University of Calgary, Alberta, Canada.
authors.forename: P Y Billie
authors.initials: PY
authors.lastname: Au
authors.forename: Hilary E
authors.initials: HE
authors.lastname: Racher
authors.forename: John M
authors.initials: JM
authors.lastname: Graham
authors.forename: Nancy
authors.initials: N
authors.lastname: Kramer
authors.forename: R Brian
authors.initials: RB
authors.lastname: Lowry
authors.forename: Jillian S
authors.initials: JS
authors.lastname: Parboosingh
authors.forename: A Micheil
authors.initials: AM
authors.lastname: Innes
mesh_terms: D054119:Arachnodactyly / Q000175:diagnosis* / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D003398:Craniosynostoses / Q000175:diagnosis* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D019066:Facies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013116:Spinal Cord / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C060614:SKI protein, human
keywords: Loeys-Dietz; Marfan; SKI protein; Shprintzen-Goldberg; aortic diseases; craniosynostosis; human; transforming growth factor beta