Phenotypic heterogeneity of Marfan-like connective tissue disorders associated with mutations in the transforming growth factor-beta receptor genes.

Abstract

BACKGROUND:

Mutations in the genes for transforming growth factor-beta receptor (TGFBR) have been identified in patients with Marfan syndrome (MFS) and Marfan-like connective tissue disorders. There are several syndromes associated with mutations in TGFBR genes, including Loeys-Dietz syndrome (LDS), MFS2, Furlong syndrome, and Shprintzen-Goldberg syndrome. However, with the exception of the first report by Loeys et al, the phenotypic features of patients with TGFBR gene mutations have not been precisely reported.

METHODS AND RESULTS:

A total of 18 patients suspected of having MFS were recruited and 7 were diagnosed with MFS and mutations in FBN1. Among the remaining 11 patients, 1 patient had mutations in TGFBR1, 2 had mutations in TGFBR2, and 1 had mutations in COL3A1. The clinical manifestations of the 3 patients with TGFBR gene mutations were examined according to the list of 36 clinical features described in the first report by Loeys et al. The clinical manifestations of these 3 patients differed from those previously observed in patients with MFS2, Furlong syndrome, and Shprintzen-Goldberg syndrome. Thus, the most probable diagnosis of these 3 patients was LDS, despite the fact that they presented with only a fraction of the 36 clinical features associated with LDS.

CONCLUSIONS:

Although the number of the patients was limited, the findings support the notion that mutations in the TGFBR gene may be associated with greater phenotypic heterogeneity than previously reported.

• Authors: Koichi Akutsu, Hiroko Morisaki, Satoshi Takeshita, Shingo Sakamoto, Yuiichi Tamori, Tsuyoshi Yoshimuta, Naoyuki Yokoyama, Hiroshi Nonogi, Hitoshi Ogino, Takayuki Morisaki
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 71 Issue 8 Pg. 1305-9 (Aug 2007) ISSN: 1346-9843 [Print] Japan
• PMID: 17652900 (Publication Type: Case Reports, Journal Article)

Chemical References

• COL3A1 protein, human
• Collagen Type III
• FBN1 protein, human
• Fibrillin-1
• Fibrillins
• Microfilament Proteins
• Receptors, Transforming Growth Factor beta
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II
• TGFBR1 protein, human

Topics

• Adult
• Collagen Type III (genetics)
• Connective Tissue Diseases (diagnosis, genetics)
• DNA Mutational Analysis
• Female
• Fibrillin-1
• Fibrillins
• Humans
• Male
• Marfan Syndrome (diagnosis, genetics)
• Microfilament Proteins (genetics)
• Mutation
• Phenotype
• Protein Serine-Threonine Kinases (genetics)
• Receptor, Transforming Growth Factor-beta Type I
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (genetics)