Genotype FBN1/phenotype relationship in a cohort of patients with Marfan syndrome.

Autores de IIS La Fe

• Amparo Hernándiz Martínez

  Autor

• Ángel Zúñiga Cabrera

  Autor

• Francisco José Valera Martínez

  Autor

• Diana Domingo Valero

  Autor

• Imelda Ontoria Oviedo

  Autor

• Francisco Jose Mari Cotino

  Autor

• 

  José Andrés Román Ivorra

  Autor

• 

  Inmaculada Calvo Penadés

  Autor

• Beatriz Insa Albert

  Autor

• José Vicente Cervera Zamora

  Autor

• Manuel Miralles Hernández

  Autor

• José Anastasio Montero Argudo

  Autor

• 

  Luis Vicente Martínez Dolz

  Autor

• 

  Pilar Sepúlveda Sanchis

  Autor

Participantes ajenos a IIS La Fe

• Gómez R

Grupos

• Cardiopatías familiares, muerte súbita y mecanismos de enfermedad (CAFAMUSME)

• Grupo de Investigación Clínica y Traslacional en Cardiología

• Hematología y Hemoterapia

• Hemostasia, Trombosis, Arteriosclerosis y Biología vascular

• Regeneración y Trasplante Cardíaco

• Reumatología

• Reumatología Pediátrica

Abstract

Marfan syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene, and cardiovascular involvement is the leading cause of mortality. We sought to examine the genotype/phenotype realtionship in 61 consecutive patients with a phenotype and genotype compatible with MFS. The FBN1 gene was analyzed by massive sequencing using a hybridization capture-based target enrichment custom panel. Forty-three different variants of FBN1 were identified, of which 17 have not been previously reported. The causal variants of MFS were grouped into mutations resulting in haploinsufficiency (HI group; 23 patients) and mutations producing a dominant-negative effect (DN group; 38 patients). Patient information was collected from electronic medical records and clinical evaluation. While no significant differences were found between the two groups, the HI group included more cases with aortic dissection and occurring at a younger age that the DN group (34.7% vs. 15.8%; p = 0.160). Irrespective of the mutation group, males presented with a higher probability of aortic involvement (4-fold higher risk than females) and aortic dissections events occurred at younger ages. Patients with DN variants carrying a cysteine substitution had a higher incidence of ectopia lentis.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords

• FBN1; Marfan syndrome; aortic dissection; gender