Heterozygous TGFBR2 mutations in Marfan syndrome.

Takeshi Mizuguchi; Gwenaëlle 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

doi:10.1038/ng1392

Journal articles

Heterozygous TGFBR2 mutations in Marfan syndrome.

Takeshi Mizuguchi ^{1, 2} Gwenaëlle Collod-Beroud ^{3, 4} Takushi Akiyama ⁵ Marianne Abifadel ⁴ Naoki Harada ^{1, 2} Takayuki Morisaki ⁶ Delphine Allard ⁴ Mathilde Varret ⁴ Mireille Claustres ³ Hiroko Morisaki ⁶ Makoto Ihara ⁷ Akira Kinoshita ^{1, 2} Koh-Ichiro Yoshiura ^{1, 2} Claudine Junien ^{4, 8} Tadashi Kajii ⁹ Guillaume Jondeau ^{4, 10} Tohru Ohta ^{2, 11, 12} Tatsuya Kishino ^{2, 11} Yoichi Furukawa ¹³ Yusuke Nakamura ¹³ Norio Niikawa ^{1, 2} Catherine Boileau ^{4, *} Naomichi Matsumoto ^{1, 2, 14, *}

* Corresponding author

1 Department of Human Genetics

2 CREST - Core Research for Evolutional Science and Technology

3 IGH - Institut de génétique humaine

4 Génétique, chromosome et cancer

5 Division of Pediatric Surgery

6 Department of Bioscience

7 Department of Radiation Biophysics

8 Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré]

9 Hachioji

10 Service de cardiologie et maladies vasculaires [CHU Ambroise Paré]

11 Division of Functional Genomics, Center for Frontier Life Sciences

12 The Research Institute of Personalized Health Sciences

13 Human Genome Center, Institute of Medical Science

14 Department of Human Genetics

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Genetics

Complete list of metadatas

Cited literature [21 references] Display Hide Download

https://www.hal.inserm.fr/inserm-00143367
Contributor : Gwenaëlle Collod-Beroud <>
Submitted on : Friday, April 27, 2007 - 9:10:29 AM
Last modification on : Wednesday, August 19, 2020 - 11:16:44 AM
Long-term archiving on: : Wednesday, April 7, 2010 - 3:26:29 AM

Heterozygous TGFBR2 mutations in Marfan syndrome.

Files

Identifiers

Citation

Export

Metrics

260

528

Heterozygous TGFBR2 mutations in Marfan syndrome.

Files

Identifiers

Citation

Export

Share

Metrics

260

528