Cardiovascular manifestations in men and women carrying a FBN1 mutation

Détaint, Delphine; Faivre, Laurence; Collod‐Béroud, Gwenaëlle; Child, Anne H.; Loeys, Bart; Binquet, Christine; Gautier, Élodie; Arbustini, Eloisa; Mayer, Karin; Arslan‐Kirchner, Mine; Stheneur, Chantal; Halliday, Dorothy; Béroud, Christophe; Bonithon‐Kopp, Claire; Claustres, Mireille; Plauchu, Henri; Robinson, Peter N.; Kiotsekoglou, Anatoli; Backer, Julie De; Adès, Lesley C.; Francke, Uta; Paepe, Anne De; Boileau, Cathérine; Jondeau, Guillaume

doi:10.1093/eurheartj/ehq258

Cited by 135 publications

(102 citation statements)

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“…1 We also observed that patients with aortic dissection had a higher frequency of a protein-truncating or -splicing variant (86%) as compared with patients with prophylactic aortic surgery (69%), although this observation was not statistically significant. In addition, we noted a trend in association between genotype and age at aortic surgery, dissection, or both.…”

Section: Discussionmentioning

confidence: 63%

“…Détaint et al 1 previously reported on cardiovascular manifestations in 1,013 probands with pathogenic FBN1 mutations. They observed that the probability of an aortic event before the age of 30 years in their cohort was 16% in men and 11% in women; before the age of 40 years this probability was ~40-45% in men and 25% in women.…”

Section: Resultsmentioning

confidence: 99%

“…Détaint et al 1 observed a higher probability of ascending aortic dilatation, aortic event, and mitral valve prolapse in patients with mutations altering a cysteine residue. However, their published analysis did not split out aortic dissection or aortic surgery alone and genotype.…”

Section: Discussionmentioning

confidence: 99%

“…However, it should be noted that the frequency of aortic events in our cohort was similar to that reported by another larger study. Specifically, Détaint et al 1 observed a frequency of aortic events in 279 of 965 (28.9%) FBN1 mutation-positive patients ages 11 and older. We observed a similar aortic event frequency of 27.4% (34 of 124) in our cohort, considering patients ages 11 and older.…”

Section: Discussionmentioning

confidence: 99%

“…A study investigating genotype-phenotype correlations with cardiovascular features did not observe significant differences with mutation type (e.g., frameshift versus missense) but did observe a higher probability of ascending aortic dilatation, aortic event, and mitral valve prolapse in patients with mutations altering a cysteine residue. 1 The type of FBN1 mutation identified and its likelihood of being pathogenic are recognized as important factors when making a diagnosis of MFS and later clinical decisions. Some have argued that truncating and splicing mutations may be associated with a milder disease course.…”

mentioning

confidence: 99%

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Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic events

Baudhuin

Kotzer

Lagerstedt

2015

Genetics in Medicine

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Original research article introduction FBN1 mutations are most commonly associated with Marfan syndrome (MFS), an autosomal dominant connective tissue disorder typically involving the ocular, skeletal, and cardiovascular systems; MFS less frequently involves the skin, integument, lung, muscle, and adipose tissue. Cardiovascular manifestations, which are the major cause of morbidity and early mortality in MFS, include aortic dilatation at the level of the sinus of Valsalva, predisposition for aortic dissection, mitral valve and tricuspid valve prolapse, and enlargement of the proximal pulmonary artery.In MFS, an age-dependent association with the occurrence of an aortic event (aortic dissection or prophylactic aortic surgery) has been demonstrated in 16% of 30-year-olds and 74% of 60-year-olds having an aortic event.1 A sex-dependent association has also been observed: aortic events occur at an earlier age in males than in females. 1Hundreds of mutations have been identified in FBN1-many of them unique to individual families. Missense mutations are the most common type of FBN1 mutation, the majority of which are cysteine substitutions. FBN1 mutations have been shown to occur across the gene with limited genotypephenotype correlations, with the exception of the association of early onset, severe (previously termed "neonatal") MFS and mutations in exons 24 through 32, as well as the association of ectopia lentis with missense mutations. A study investigating genotype-phenotype correlations with cardiovascular features did not observe significant differences with mutation type (e.g., frameshift versus missense) but did observe a higher probability of ascending aortic dilatation, aortic event, and mitral valve prolapse in patients with mutations altering a cysteine residue. 1The type of FBN1 mutation identified and its likelihood of being pathogenic are recognized as important factors when making a diagnosis of MFS and later clinical decisions. Some have argued that truncating and splicing mutations may be associated with a milder disease course. Accordingly, we evaluated 179 consecutive probands with FBN1 mutations to evaluate this important clinical issue. MAtEriALS And MEtHodS Study populationProband samples (n = 179) with a pathogenic or likely pathogenic FBN1 variant and detailed clinical information received over a 4.25-year period were included in this study. Each patient was examined by his or her referring physician. For Mayo Clinic patients, phenotypic information was extracted from the patients' electronic medical record. For patients external to the Mayo Clinic, phenotypic information was provided by the referring provider via a requisition form specific to FBN1, which included age, sex, suspected diagnosis, family history, and phenotypic features, including those related to the Ghent (2010 revised) nosology criteria. Purpose: Marfan syndrome is a systemic disorder that typically involves FBN1 mutations and cardiovascular manifestations. We investigated FBN1 genotype-phenotype correlations with aortic eve...

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Section: Discussionmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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