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Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome.

Bart Loeys UGent, Lieve Nuytinck UGent, Isabelle Delvaux, Sylvia De Bie and Anne De Paepe UGent (2001) ARCHIVES OF INTERNAL MEDICINE. 161(20). p.2447-2454
abstract
Background: Marfan syndrome (MFS) is an underrecognized heritable connective tissue disorder resulting from mutations in the gene for fibrillin-1 (FBN1). Affected patients are at risk for aortic dissection and/or severe ocular and orthopedic problems. The diagnosis is primarily based on a set of well-defined clinical criteria (Ghent nosology). The age-related nature of some clinical manifestations and variable phenotypic expression may hinder the diagnosis, particularly in children. Molecular analysis may be helpful to identify at-risk individuals early and start prophylactic medical treatment. FBN1 mutations have also been reported in patients with Marfan-related conditions, but it is unknown what proportion of all FBN1 mutation carriers they represent. Methods: We reviewed the clinical and molecular data of 171 consecutive patients referred for FBN1 analysis because either MFS was diagnosed or they had signs suggestive of MFS. We compared the incidence of mutations in patients who fulfilled the clinical diagnostic criteria for MFS with those who did not. Results: Diagnostic criteria for MFS were fulfilled in 94 patients, 62 (66%) of whom had an FBN1 mutation. A significantly higher incidence of ectopia lentis was found in the patients with MFS with an FBN1 mutation vs those without (P=.04). Among the 77 patients who did not meet the criteria, an FBN1 mutation was found in 9 patients (12%). No correlation was found between the severity of the phenotype and the position and nature of the FBN1 mutation. Conclusions: This study showed a significant difference in the number of FBN1 mutations between patients fulfilling and those not fulfilling the diagnostic criteria for MFS, which seems to be a good predictor of the presence of an FBN1 mutation. A comprehensive clinical evaluation is mandatory before establishing a definitive diagnosis. An FBN1 mutation analysis is helpful to identify individuals at high risk for MFS who need careful follow-up, particularly in families displaying phenotypic variability and in children.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
journal title
ARCHIVES OF INTERNAL MEDICINE
Arch. Intern. Med.
volume
161
issue
20
pages
2447-2454 pages
Web of Science type
Article
Web of Science id
000172055700006
JCR category
MEDICINE, GENERAL & INTERNAL
JCR impact factor
6.661 (2001)
JCR rank
6/108 (2001)
JCR quartile
1 (2001)
ISSN
0003-9926
language
English
UGent publication?
yes
classification
A1
id
141107
handle
http://hdl.handle.net/1854/LU-141107
date created
2004-01-14 13:37:00
date last changed
2016-12-19 15:38:04
@article{141107,
  abstract     = {Background: Marfan syndrome (MFS) is an underrecognized heritable connective tissue disorder resulting from mutations in the gene for fibrillin-1 (FBN1). Affected patients are at risk for aortic dissection and/or severe ocular and orthopedic problems. The diagnosis is primarily based on a set of well-defined clinical criteria (Ghent nosology). The age-related nature of some clinical manifestations and variable phenotypic expression may hinder the diagnosis, particularly in children. Molecular analysis may be helpful to identify at-risk individuals early and start prophylactic medical treatment. FBN1 mutations have also been reported in patients with Marfan-related conditions, but it is unknown what proportion of all FBN1 mutation carriers they represent.

Methods: We reviewed the clinical and molecular data of 171 consecutive patients referred for FBN1 analysis because either MFS was diagnosed or they had signs suggestive of MFS. We compared the incidence of mutations in patients who fulfilled the clinical diagnostic criteria for MFS with those who did not.

Results: Diagnostic criteria for MFS were fulfilled in 94 patients, 62 (66\%) of whom had an FBN1 mutation. A significantly higher incidence of ectopia lentis was found in the patients with MFS with an FBN1 mutation vs those without (P=.04). Among the 77 patients who did not meet the criteria, an FBN1 mutation was found in 9 patients (12\%). No correlation was found between the severity of the phenotype and the position and nature of the FBN1 mutation.

Conclusions: This study showed a significant difference in the number of FBN1 mutations between patients fulfilling and those not fulfilling the diagnostic criteria for MFS, which seems to be a good predictor of the presence of an FBN1 mutation. A comprehensive clinical evaluation is mandatory before establishing a definitive diagnosis. An FBN1 mutation analysis is helpful to identify individuals at high risk for MFS who need careful follow-up, particularly in families displaying phenotypic variability and in children.},
  author       = {Loeys, Bart and Nuytinck, Lieve and Delvaux, Isabelle and De Bie, Sylvia and De Paepe, Anne},
  issn         = {0003-9926},
  journal      = {ARCHIVES OF INTERNAL MEDICINE},
  language     = {eng},
  number       = {20},
  pages        = {2447--2454},
  title        = {Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome.},
  volume       = {161},
  year         = {2001},
}

Chicago
Loeys, Bart, Lieve Nuytinck, Isabelle Delvaux, Sylvia De Bie, and Anne De Paepe. 2001. “Genotype and Phenotype Analysis of 171 Patients Referred for Molecular Study of the Fibrillin-1 Gene FBN1 Because of Suspected Marfan Syndrome.” Archives of Internal Medicine 161 (20): 2447–2454.
APA
Loeys, Bart, Nuytinck, L., Delvaux, I., De Bie, S., & De Paepe, A. (2001). Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome. ARCHIVES OF INTERNAL MEDICINE, 161(20), 2447–2454.
Vancouver
1.
Loeys B, Nuytinck L, Delvaux I, De Bie S, De Paepe A. Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome. ARCHIVES OF INTERNAL MEDICINE. 2001;161(20):2447–54.
MLA
Loeys, Bart, Lieve Nuytinck, Isabelle Delvaux, et al. “Genotype and Phenotype Analysis of 171 Patients Referred for Molecular Study of the Fibrillin-1 Gene FBN1 Because of Suspected Marfan Syndrome.” ARCHIVES OF INTERNAL MEDICINE 161.20 (2001): 2447–2454. Print.