Heterozygous TGFBR2 Mutations in Marfan Syndrome

Overview

Journal Nat Genet

Specialty Genetics

Date 2004 Jul 6

PMID 15235604

Citations 208

Authors

Takeshi Mizuguchi

Gwenaelle Collod-Beroud

Takushi Akiyama

Marianne Abifadel

Naoki Harada

Takayuki Morisaki

Delphine Allard

Mathilde Varret

Mireille Claustres

Hiroko Morisaki

Makoto Ihara

Akira Kinoshita

Koh-Ichiro Yoshiura

Claudine Junien

Tadashi Kajii

Guillaume Jondeau

Tohru Ohta

Tatsuya Kishino

Yoichi Furukawa

Yusuke Nakamura

Norio Niikawa

Catherine Boileau

Naomichi Matsumoto

Affiliations

Soon will be listed here.

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.

Citing Articles

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