title: Duplication of the TGFBR1 gene causes features of Loeys-Dietz syndrome.
abstract: Loeys-Dietz syndrome (LDS; OMIM:609192) is an autosomal dominant disorder characterized by hypertelorism, bifid uvula or cleft palate, and arterial tortuosity with widespread vascular aneurysms and a high risk of aortic dissection at an early age. LDS results from mutations in the transforming growth factor beta-receptor I and II (TGFBR1 and TGFBR2) genes, altering the transmission of the subcellular TGF-β signal, mediated by increased activation of Smad2. We report on a 17-year-old boy with pubertas tarda, a bifid uvula, camptodactyly and facial dysmorphic features, suggestive of LDS. Mutation analysis of TGFBR1 and TGFBR2 was normal. By means of molecular karyotyping two previously unreported chromosomal imbalances were detected: a 120 kb deletion on chromosome 22q13.31q13.32, inherited from an unaffected parent, and a de novo 14.6 Mb duplication on chromosome 9q22.32q31.3, comprising TGFBR1. We hypothesize that copy number gain of TGFBR1 contributes to the phenotype.
authors.affiliation: Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Breckpot
authors.forename: Werner
authors.initials: W
authors.lastname: Budts
authors.forename: Francis
authors.initials: F
authors.lastname: De Zegher
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
authors.forename: Koenraad
authors.initials: K
authors.lastname: Devriendt
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D000784:Aortic Dissection / Q000235:genetics; D001014:Aortic Aneurysm / Q000235:genetics; D002872:Chromosome Deletion; D055028:Comparative Genomic Hybridization / Q000379:methods*; D019465:Craniofacial Abnormalities / Q000235:genetics; D020440:Gene Duplication; D006228:Hand Deformities, Congenital / Q000235:genetics; D006801:Humans; D055947:Loeys-Dietz Syndrome / Q000235:genetics*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human