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Mutations in Fibrillin 1 (FBN1) are associated with Marfan syndrome and in some instances with the MASS phenotype (myopia, mitral valve prolapse, borderline non-progressive aortic root dilatation, skeletal features, and striae). Potential confusion over diagnosis and management in patients with borderline features has been addressed through the revised Ghent nosology, which emphasizes the importance of aortic root dilatation and ectopia lentis as features of Marfan syndrome. The overlapping and more common mitral valve prolapse syndrome is precluded by ectopia lentis or aortic dilatation. Among these clinically related conditions, there is no compelling evidence that genotype predicts phenotype, with the exception of neonatal Marfan syndrome, mutations in which cluster within FBN1 exons 24-32. Recent reports also link two very different phenotypes to changes in FBN1. Heterozygous mutations in transforming growth factor β-binding protein-like domain 5 (TB5) can cause acromicric or geleophysic dysplasias-and mutations in the TB4 domain, which contains an integrin binding RGD loop, have been found in congenital scleroderma/stiff skin syndrome. We report on a variant in an evolutionarily conserved residue that stabilizes the integrin binding fragment of FBN1, associated with juvenile idiopathic arthritis, mitral valve prolapse or apparently normal phenotype in different family members.

Original publication

DOI

10.1002/ajmg.a.36011

Type

Journal article

Journal

Am J Med Genet A

Publication Date

08/2013

Volume

161A

Pages

2047 - 2051

Keywords

Marfan syndrome, fibrillin 1, juvenile idiopathic arthritis, mitral valve prolapse, Adolescent, Adult, Amino Acid Sequence, Arthritis, Juvenile, Female, Fibrillin-1, Fibrillins, Humans, Integrins, Male, Microfilament Proteins, Mitral Valve Prolapse, Molecular Sequence Data, Mutation, Pedigree, Phenotype, Protein Conformation, Sequence Homology, Amino Acid, Young Adult