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Marfan syndrome: ocular findings and novel mutations—in pursuit of genotype–phenotype associations

      Abstract

      Objective

      To analyze ocular involvement in patients diagnosed with Marfan syndrome (MFS), study their clinical findings and prognosis based on the type of FBN1 mutation, and evaluate possible genotype–phenotype correlations.

      Design

      Observational single-centre case series.

      Participants

      Eleven patients diagnosed with MFS were included. All subjects met the Ghent criteria of MFS, the diagnosis was confirmed by genetic testing.

      Methods

      All subjects underwent a complete ophthalmologic examination. We evaluated clinical data, the incidence of ectopia lentis (EL), and other eye disorders. The association of ocular signs with the type of mutation was analyzed.

      Results

      Four of the 11 patients had EL, of which 3 developed secondary glaucoma, and 62.5% of the phakic patients had myopia. Other ocular abnormalities included strabismus, retinal tears, retinal detachment, and amblyopia. The encountered types of mutations were premature termination codon (PTC) in 7 patients, missense in 2 cases, 1 aberration of splicing, and 1 indel mutation. Two novel mutations were found. Of the patients with EL, 2 had a missense, 1 an indel, and 1 a nonsense mutation.

      Conclusions

      Myopia was the most frequent ocular involvement. Patients with a PTC mutation revealed to have a smaller risk of EL; however, more studies are required to indicate the mechanism of the correlation.

      Résumé

      Objectif

      Analyser l'atteinte oculaire chez les patients ayant reçu un diagnostic du syndrome de Marfan (MFS), étudier leurs résultats cliniques et le pronostic en fonction du type de mutation dans le gène FNBN1 et évaluer les corrélations génotype-phénotype possibles.

      Nature

      Observation d’une série de cas dans un seul centre.

      Participants

      11 patients ayant reçu un diagnostic du syndrome de Marfan. Tous les sujets répondaient aux critères de Gand du syndrome de Marfan, et le diagnostic a été confirmé par des tests génétiques.

      Méthodes

      Tous les sujets ont subi un examen ophtalmologique complet. Nous avons évalué les données cliniques et l'incidence de l'ectopie du cristallin (EC) et d'autres troubles oculaires. Nous avons aussi analysé les liens entre les signes oculaires et le type de mutation.

      Résultats

      4 des 11 patients avaient une EC, dont 3 ont développé un glaucome secondaire. 62,5 % des patients phaques étaient myopes. Entre autres anomalies oculaires constatées, mentionnons le strabisme, des déchirures rétiniennes, un décollement de la rétine et l'amblyopie. Nous avons constaté les types de mutation. suivants: 7 cas de terminaison prématurée du codon, 2 cas de faux-sens, 1 cas d'aberration de l'épissage et 1 de mutation indel. Deux nouveaux types de mutations ont été trouvées. Chez les patients atteints d'EC, nous avons relevé 2 cas de faux-sens, 1 cas d'indel et 1 cas de non-sens.

      Conclusions

      La myopie est l'atteinte oculaire la plus fréquente. Les patients chez qui nous avons constaté une terminaison prématurée du codon couraient un risque plus faible d'EC, mais d'autres études sont nécessaires pour déterminer le mécanisme de la corrélation.
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