Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for marfan syndrome

Further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion

L. Faivre, G. Collod-Beroud, B. Callewaert, A. Child, B. L. Loeys, C. Binquet, E. Gautier, E. Arbustini, K. Mayer, M. Arslan-Kirchner, A. Kiotsekoglou, P. Comeglio, M. Grasso, C. Beroud, C. Bonithon-Kopp, M. Claustres, C. Stheneur, O. Bouchot, J. E. Wolf, P. N. Robinson & 7 others L. Ades, J. De Backer, P. Coucke, U. Francke, A. De Paepe, C. Boileau, G. Jondeau

Research output: Contribution to journalArticle

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Abstract

Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with ''other type I fibrillinopathy.'' In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete ''clinical'' international criteria (Ghent nosology) from a large collaborative international study including 1,009 propositi with a pathogenic FBN1 mutation. We focused on patients with only one major clinical criterion, [including isolated ectopia lentis (EL; 12 patients), isolated ascending aortic dilatation (17 patients), and isolated major skeletal manifestations (1 patient)] or with no major criterion but only minor criteria in 1 or more organ systems (16 patients). At least one component of the Ghent nosology, insufficient alone to make a minor criterion, was found in the majority of patients with isolated ascending aortic dilatation and isolated EL. In patients with isolated EL, missense mutations involving a cyste- ine were predominant, mutations in exons 24-32 were under- represented, and no mutations leading to a premature truncation were found. Studies of recurrent mutations and affected family members of propositi with only one major clinical criterion argue for a clinical continuum between such phenotypes and classical MFS. Using strict definitions, we conclude that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.

Original languageEnglish
Pages (from-to)854-860
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume149
Issue number5
DOIs
Publication statusPublished - May 2009

Fingerprint

Marfan Syndrome
Mutation
Dilatation
Phenotype
Missense Mutation
Cysteine
Exons

Keywords

  • Fbn1 gene
  • International criteria
  • Marfan syndrome
  • Type i fibrillinopathy

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for marfan syndrome : Further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion. / Faivre, L.; Collod-Beroud, G.; Callewaert, B.; Child, A.; Loeys, B. L.; Binquet, C.; Gautier, E.; Arbustini, E.; Mayer, K.; Arslan-Kirchner, M.; Kiotsekoglou, A.; Comeglio, P.; Grasso, M.; Beroud, C.; Bonithon-Kopp, C.; Claustres, M.; Stheneur, C.; Bouchot, O.; Wolf, J. E.; Robinson, P. N.; Ades, L.; De Backer, J.; Coucke, P.; Francke, U.; De Paepe, A.; Boileau, C.; Jondeau, G.

In: American Journal of Medical Genetics, Part A, Vol. 149, No. 5, 05.2009, p. 854-860.

Research output: Contribution to journalArticle

Faivre, L, Collod-Beroud, G, Callewaert, B, Child, A, Loeys, BL, Binquet, C, Gautier, E, Arbustini, E, Mayer, K, Arslan-Kirchner, M, Kiotsekoglou, A, Comeglio, P, Grasso, M, Beroud, C, Bonithon-Kopp, C, Claustres, M, Stheneur, C, Bouchot, O, Wolf, JE, Robinson, PN, Ades, L, De Backer, J, Coucke, P, Francke, U, De Paepe, A, Boileau, C & Jondeau, G 2009, 'Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for marfan syndrome: Further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion', American Journal of Medical Genetics, Part A, vol. 149, no. 5, pp. 854-860. https://doi.org/10.1002/ajmg.a.32809
Faivre, L. ; Collod-Beroud, G. ; Callewaert, B. ; Child, A. ; Loeys, B. L. ; Binquet, C. ; Gautier, E. ; Arbustini, E. ; Mayer, K. ; Arslan-Kirchner, M. ; Kiotsekoglou, A. ; Comeglio, P. ; Grasso, M. ; Beroud, C. ; Bonithon-Kopp, C. ; Claustres, M. ; Stheneur, C. ; Bouchot, O. ; Wolf, J. E. ; Robinson, P. N. ; Ades, L. ; De Backer, J. ; Coucke, P. ; Francke, U. ; De Paepe, A. ; Boileau, C. ; Jondeau, G. / Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for marfan syndrome : Further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion. In: American Journal of Medical Genetics, Part A. 2009 ; Vol. 149, No. 5. pp. 854-860.
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