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Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome

Bart Loeys (UGent) , Julie De Backer (UGent) , Petra Van Acker (UGent) , Karen Wettinck (UGent) , G PALS, Lieve Nuytinck (UGent) , Paul Coucke (UGent) and Anne De Paepe (UGent)
(2004) HUMAN MUTATION. 24(2). p.140-146
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Abstract
In order to estimate the contribution of mutations at the fibrillin,1 locus (FBN1) to classical Marfan syndrome (MFS) and to study possible phenotypic differences between patients with an FBN1 mutation vs. without, a comprehensive molecular study of the FBN1 gene in a cohort of 93 MFS patients fulfilling the clinical diagnosis of MFS according to the Ghent nosology was performed. The initial mutation screening by CSGE/SSCP allowed identification of an FBN1-mutation in 73 patients. Next, sequencing of all FBN1-exons was performed in 11 mutation-negative patients, while in nine others, DHPLC was used. This allowed identification of seven and five additional mutations, respectively. Southern blot analysis revealed an abnormal hybridization pattern in one more patient. A total of 23 out of the 85 mutations identified here are reported for the first time. Phenotypic comparison of MFS patients with cysteine-involving mutations vs. premature termination mutations revealed significant differences in ocular and skeletal involvement. The phenotype of the eight patients without proven FBN1 mutation did not differ from the others With respect to the presence of major cardiac, ocular, and skeletal manifestations or positive familial history. Most likely, a portion of FBN1-mutations remains undetected because of technical limitations. In conclusion, the involvement of the FBN1-gene could be demonstrated in at least 91% of all MFS patients (85/93), which strongly suggests that this gene is the predominant, if not the sole, locus for MFS.

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Chicago
Loeys, Bart, Julie De Backer, Petra Van Acker, Karen Wettinck, G PALS, Lieve Nuytinck, Paul Coucke, and Anne De Paepe. 2004. “Comprehensive Molecular Screening of the FBN1 Gene Favors Locus Homogeneity of Classical Marfan Syndrome.” Human Mutation 24 (2): 140–146.
APA
Loeys, Bart, De Backer, J., Van Acker, P., Wettinck, K., PALS, G., Nuytinck, L., Coucke, P., et al. (2004). Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome. HUMAN MUTATION, 24(2), 140–146.
Vancouver
1.
Loeys B, De Backer J, Van Acker P, Wettinck K, PALS G, Nuytinck L, et al. Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome. HUMAN MUTATION. WILEY-LISS; 2004;24(2):140–6.
MLA
Loeys, Bart, Julie De Backer, Petra Van Acker, et al. “Comprehensive Molecular Screening of the FBN1 Gene Favors Locus Homogeneity of Classical Marfan Syndrome.” HUMAN MUTATION 24.2 (2004): 140–146. Print.
@article{303673,
  abstract     = {In order to estimate the contribution of mutations at the fibrillin,1 locus (FBN1) to classical Marfan syndrome (MFS) and to study possible phenotypic differences between patients with an FBN1 mutation vs. without, a comprehensive molecular study of the FBN1 gene in a cohort of 93 MFS patients fulfilling the clinical diagnosis of MFS according to the Ghent nosology was performed. The initial mutation screening by CSGE/SSCP allowed identification of an FBN1-mutation in 73 patients. Next, sequencing of all FBN1-exons was performed in 11 mutation-negative patients, while in nine others, DHPLC was used. This allowed identification of seven and five additional mutations, respectively. Southern blot analysis revealed an abnormal hybridization pattern in one more patient. A total of 23 out of the 85 mutations identified here are reported for the first time. Phenotypic comparison of MFS patients with cysteine-involving mutations vs. premature termination mutations revealed significant differences in ocular and skeletal involvement. The phenotype of the eight patients without proven FBN1 mutation did not differ from the others With respect to the presence of major cardiac, ocular, and skeletal manifestations or positive familial history. Most likely, a portion of FBN1-mutations remains undetected because of technical limitations. In conclusion, the involvement of the FBN1-gene could be demonstrated in at least 91\% of all MFS patients (85/93), which strongly suggests that this gene is the predominant, if not the sole, locus for MFS.},
  author       = {Loeys, Bart and De Backer, Julie and Van Acker, Petra and Wettinck, Karen and PALS, G and Nuytinck, Lieve and Coucke, Paul and De Paepe, Anne},
  issn         = {1059-7794},
  journal      = {HUMAN MUTATION},
  language     = {eng},
  number       = {2},
  pages        = {140--146},
  publisher    = {WILEY-LISS},
  title        = {Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome},
  url          = {http://dx.doi.org/10.1002/humu.20070},
  volume       = {24},
  year         = {2004},
}

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