title: Skeletal manifestations of Marfan syndrome associated to heterozygous R2726W FBN1 variant: sibling case report and literature review.
abstract: BACKGROUND
  FBN1 (15q21.1) encodes fibrillin-1, a large glycoprotein which is a major component of microfibrils that are widely distributed in structural elements of elastic and non-elastic tissues. FBN1 variants are responsible for the related connective tissue disorders, grouped under the generic term of type-1 fibrillinopathies, which include Marfan syndrome (MFS), MASS syndrome (Mitral valve prolapse, Aortic enlargement, Skin and Skeletal findings, Acromicric dysplasia, Familial ectopia lentis, Geleophysic dysplasia 2, Stiff skin syndrome, and dominant Weill-Marchesani syndrome.
  
  
  METHODS
  Two siblings presented with isolated skeletal manifestations of MFS, including severe pectus excavatum, elongated face, scoliosis in one case, and absence of other clinical features according to Ghent criteria diagnosis, were screened for detection of variants in whole FBN1 gene (65 exons). Both individuals were heterozygous for the R2726W variant. This variant has been previously reported in association with some skeletal features of Marfan syndrome in the absence of both tall stature and non-skeletal features. These features are consistent with the presentation of the siblings reported here.
  
  
  CONCLUSIONS
  The presented cases confirm that the R2726W FBN1 variant is associated with skeletal features of MFS in the absence of cardiac or ocular findings. These findings confirm that FBN1 variants are associated with a broad phenotypic spectrum and the value of sequencing in atypical cases.
authors.affiliation: Laboratorio de Genética y Diagnóstico Molecular, Hospital Juárez de México, Instituto Politécnico Nacional 5160, Gustavo A. Madero, Magdalena de Las Salinas, Ciudad de México, DF, 07760, Mexico. maiden_sp@yahoo.com.mx.
authors.forename: Octavio D
authors.initials: OD
authors.lastname: Reyes-Hernández
authors.affiliation: Laboratorio de Genética y Diagnóstico Molecular, Hospital Juárez de México, Instituto Politécnico Nacional 5160, Gustavo A. Madero, Magdalena de Las Salinas, Ciudad de México, DF, 07760, Mexico. cyapalacios@gmail.com.
authors.forename: Carmen
authors.initials: C
authors.lastname: Palacios-Reyes
authors.affiliation: Laboratorio de Genética y Diagnóstico Molecular, Hospital Juárez de México, Instituto Politécnico Nacional 5160, Gustavo A. Madero, Magdalena de Las Salinas, Ciudad de México, DF, 07760, Mexico. soncargen@yahoo.com.mx.
authors.forename: Sonia
authors.initials: S
authors.lastname: Chávez-Ocaña
authors.affiliation: Laboratorio de Genética y Diagnóstico Molecular, Hospital Juárez de México, Instituto Politécnico Nacional 5160, Gustavo A. Madero, Magdalena de Las Salinas, Ciudad de México, DF, 07760, Mexico. emcortes@cinvestav.mx.
authors.forename: Enoc M
authors.initials: EM
authors.lastname: Cortés-Malagón
authors.affiliation: Seguimiento Pediátrico, Instituto Nacional de Perinatología, Montes Urales 800 Col. Lomas de Chapultepec, Del. Miguel Hidalgo, 11000, Ciudad de México, Mexico. pgalonsot@yahoo.com.
authors.forename: Patricia Garcia
authors.initials: PG
authors.lastname: Alonso-Themann
authors.affiliation: Servicio de Cirugía Cardio-torácica, Hospital Juárez de México. Av, Instituto Politécnico Nacional 5160, Gustavo A. Madero, Magdalena de Las Salinas, 07760, Ciudad de México, Mexico. nihonnoryuu@yahoo.co.jp.
authors.forename: Víctor
authors.initials: V
authors.lastname: Ramos-Cano
authors.affiliation: Laboratorio de Medicina Genómica, Hospital Juárez de México, Instituto Politécnico Nacional 5160, Gustavo A. Madero, Magdalena de Las Salinas, 07760, Ciudad de México, Mexico. dr.julian.ramirez.inv@gmail.com.
authors.forename: Julián
authors.initials: J
authors.lastname: Ramírez-Bello
authors.affiliation: Laboratorio de Genética y Diagnóstico Molecular, Hospital Juárez de México, Instituto Politécnico Nacional 5160, Gustavo A. Madero, Magdalena de Las Salinas, Ciudad de México, DF, 07760, Mexico. sierrammtz@gmail.com.
authors.forename: Mónica
authors.initials: M
authors.lastname: Sierra-Martínez
mesh_terms: D000293:Adolescent; D001848:Bone Diseases, Developmental / Q000175:diagnosis / Q000235:genetics; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D014644:Genetic Variation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D010375:Pedigree; D035781:Siblings; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines