title: Heterozygous TGFBR2 mutations in Marfan syndrome.
abstract: Marfan syndrome is an extracellular matrix disorder with cardinal manifestations in the eye, skeleton and cardiovascular systems associated with defects in the gene encoding fibrillin (FBN1) at 15q21.1 (ref. 1). A second type of the disorder (Marfan syndrome type 2; OMIM 154705) is associated with a second locus, MFS2, at 3p25-p24.2 in a large French family (family MS1). Identification of a 3p24.1 chromosomal breakpoint disrupting the gene encoding TGF-beta receptor 2 (TGFBR2) in a Japanese individual with Marfan syndrome led us to consider TGFBR2 as the gene underlying association with Marfan syndrome at the MSF2 locus. The mutation 1524G-->A in TGFBR2 (causing the synonymous amino acid substitution Q508Q) resulted in abnormal splicing and segregated with MFS2 in family MS1. We identified three other missense mutations in four unrelated probands, which led to loss of function of TGF-beta signaling activity on extracellular matrix formation. These results show that heterozygous mutations in TGFBR2, a putative tumor-suppressor gene implicated in several malignancies, are also associated with inherited connective-tissue disorders.
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mizuguchi
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Collod-Beroud
authors.forename: Takushi
authors.initials: T
authors.lastname: Akiyama
authors.forename: Marianne
authors.initials: M
authors.lastname: Abifadel
authors.forename: Naoki
authors.initials: N
authors.lastname: Harada
authors.forename: Takayuki
authors.initials: T
authors.lastname: Morisaki
authors.forename: Delphine
authors.initials: D
authors.lastname: Allard
authors.forename: Mathilde
authors.initials: M
authors.lastname: Varret
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Hiroko
authors.initials: H
authors.lastname: Morisaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Ihara
authors.forename: Akira
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Koh-ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Claudine
authors.initials: C
authors.lastname: Junien
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kajii
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohta
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kishino
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Norio
authors.initials: N
authors.lastname: Niikawa
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000595:Amino Acid Sequence; D002893:Chromosomes, Human, Pair 3; D005260:Female; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II