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


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.
Akutsu
Koichi
K
Department of Cardiovascular Medicine, National Cardiovascular Center, Suita, Japan. koiaku@hsp.ncvc.go.jp
Morisaki
Hiroko
H
Takeshita
Satoshi
S
Sakamoto
Shingo
S
Tamori
Yuiichi
Y
Yoshimuta
Tsuyoshi
T
Yokoyama
Naoyuki
N
Nonogi
Hiroshi
H
Ogino
Hitoshi
H
Morisaki
Takayuki
T
D000328:Adult; D024061:Collagen Type III / Q000235:genetics; D003240:Connective Tissue Diseases / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D054392:Adipokines
D024061:Collagen Type III; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; C439971:COL3A1 protein, human; C000605722:FBN1 protein, human; D054392:Adipokines; C000625841:TGFBR1 protein, human