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.

Laurence Faivre 1, 2, * Gwenaëlle Collod-Beroud 3 Bert Callewaert 4 Anne Child 5 Bart Loeys 4, 6 Christine Binquet 2 Elodie Gautier 2 Eloisa Arbustini 7 Karin Mayer 8 Mine Arslan-Kirchner 9 Anatoli Kiotsekoglou 6 Paolo Comeglio 6 Maurizia Grasso 7 Christophe Béroud 3 Claire Bonithon-Kopp 2 Mireille Claustres 3 Chantal Stheneur 10, 11 Olivier Bouchot 12 Jean-Eric Wolf 12 Peter Robinson 13 Lesley Adès 14, 15, 16 Julie De Backer 4 Paul Coucke 4 Uta Francke 17 Anne De Paepe 4 Catherine Boileau 11, 18, 19 Guillaume Jondeau 18, 20
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 cysteine were predominant, mutations in exons 24-32 were underrepresented, 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.
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American Journal of Medical Genetics Part A, Wiley, 2009, 149A (5), pp.854-60. 〈10.1002/ajmg.a.32809〉
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Contributeur : Gwenaëlle Collod-Beroud <>
Soumis le : jeudi 18 juin 2009 - 14:49:31
Dernière modification le : vendredi 8 juin 2018 - 14:50:10

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Laurence Faivre, Gwenaëlle Collod-Beroud, Bert Callewaert, Anne Child, Bart Loeys, et al.. 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, Wiley, 2009, 149A (5), pp.854-60. 〈10.1002/ajmg.a.32809〉. 〈inserm-00396232〉

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