Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan-related phenotypes.

Abstract

In order to evaluate the contribution of FBN1, FBN2, TGFBR1, and TGFBR2 mutations to the Marfan syndrome (MFS) phenotype, the four genes were analyzed by direct sequencing in 49 patients with MFS or suspected MFS as a cohort study. A total of 27 FBN1 mutations (22 novel) in 27 patients (55%, 27/49), 1 novel TGFBR1 mutation in 1 (2%, 1/49), and 2 recurrent TGFBR2 mutations in 2 (4%, 2/49) were identified. No FBN2 mutation was found. Three patients with either TGFBR1 or TGFBR2 abnormality did not fulfill the Ghent criteria, but expressed some overlapping features of MFS and Loeys-Dietz syndrome (LDS). In the remaining 19 patients, either of the genes did not show any abnormalities. This study indicated that FBN1 mutations were predominant in MFS but TGFBRs defects may account for approximately 5-10% of patients with the syndrome.

• Authors: Haruya Sakai, Remco Visser, Shiro Ikegawa, Etsuro Ito, Hironao Numabe, Yoriko Watanabe, Haruo Mikami, Tatsuro Kondoh, Hiroshi Kitoh, Ryusuke Sugiyama, Nobuhiko Okamoto, Tsutomu Ogata, Riccardo Fodde, Seiji Mizuno, Kyoko Takamura, Masayuki Egashira, Nozomu Sasaki, Sachiro Watanabe, Shigeru Nishimaki, Fumio Takada, Toshiro Nagai, Yasushi Okada, Yoshikazu Aoka, Kazushi Yasuda, Mitsuji Iwasa, Shigetoyo Kogaki, Naoki Harada, Takeshi Mizuguchi, Naomichi Matsumoto
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 140 Issue 16 Pg. 1719-25 (Aug 15 2006) ISSN: 1552-4825 [Print] United States
• PMID: 16835936 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FBN1 protein, human
• FBN2 protein, human
• Fibrillin-1
• Fibrillin-2
• Fibrillins
• Microfilament Proteins
• Receptors, Transforming Growth Factor beta
• Protein Serine-Threonine Kinases
• Activin Receptors, Type I
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II
• TGFBR1 protein, human

Topics

• Activin Receptors, Type I (genetics)
• Adolescent
• Adult
• Child
• Child, Preschool
• DNA Mutational Analysis
• Female
• Fibrillin-1
• Fibrillin-2
• Fibrillins
• Humans
• Male
• Marfan Syndrome (diagnosis, genetics)
• Microfilament Proteins (genetics)
• Middle Aged
• Mutation
• Phenotype
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (genetics)