Comprehensive genetic analysis of relevant four genes in 49 patients with Marfan syndrome or Marfan-related phenotypes.
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.
Sakai
Haruya
H
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Visser
Remco
R
Ikegawa
Shiro
S
Ito
Etsuro
E
Numabe
Hironao
H
Watanabe
Yoriko
Y
Mikami
Haruo
H
Kondoh
Tatsuro
T
Kitoh
Hiroshi
H
Sugiyama
Ryusuke
R
Okamoto
Nobuhiko
N
Ogata
Tsutomu
T
Fodde
Riccardo
R
Mizuno
Seiji
S
Takamura
Kyoko
K
Egashira
Masayuki
M
Sasaki
Nozomu
N
Watanabe
Sachiro
S
Nishimaki
Shigeru
S
Takada
Fumio
F
Nagai
Toshiro
T
Okada
Yasushi
Y
Aoka
Yoshikazu
Y
Yasuda
Kazushi
K
Iwasa
Mitsuji
M
Kogaki
Shigetoyo
S
Harada
Naoki
N
Mizuguchi
Takeshi
T
Matsumoto
Naomichi
N
D030201:Activin Receptors, Type I / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; 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 / Q000235:genetics*; D054392:Adipokines
D030201:Activin Receptors, Type I; D000071838:Fibrillin-1; D000071840:Fibrillin-2; 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; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C000625841:TGFBR1 protein, human