title: TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome.
abstract: Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder characterized by manifestations in the cardiovascular, skeletal, ocular, and other organ systems. MFS type1 (MFS1) is caused by mutations in the gene encoding fibrillin (FBN1). Recently, the transforming growth factor-beta receptor-2 gene, TGFBR2, has been shown to be associated with a second type of this disorder with typically mild or absent ocular involvement (MFS type 2; MFS2). Several point mutations were found in the highly conserved serine/threonine kinase domain of TGFBR2. Mutations in both TGFBR1 and TGFBR2 are associated with Loeys-Dietz aortic aneurysm syndrome (LDS). We searched for TGFBR1 and TGFBR2 mutations in 41 unrelated patients fulfilling the diagnostic criteria of Ghent nosology or with the tentative diagnosis of Marfan syndrome, in whom mutations in the FBN1 coding region were not identified. In TGFBR1, two mutations and two polymorphisms were detected. In TGFBR2, five mutations and six polymorphisms were identified. Reexamination of patients with a TGFBR1 or TGFBR2 mutation revealed extensive clinical overlap between patients with MFS1, MFS2, and LDS.
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Krishna Kumar
authors.initials: KK
authors.lastname: Singh
authors.forename: Kathrin
authors.initials: K
authors.lastname: Rommel
authors.forename: Anjali
authors.initials: A
authors.lastname: Mishra
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmidtke
authors.forename: Mine
authors.initials: M
authors.lastname: Arslan-Kirchner
mesh_terms: D030201:Activin Receptors, Type I / Q000737:chemistry / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D017545:Aortic Aneurysm, Thoracic / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics*; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human