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- Title
Quantifying the Genetic Basis of Marfan Syndrome Clinical Variability.
- Authors
Grange, Thomas; Aubart, Mélodie; Langeois, Maud; Benarroch, Louise; Arnaud, Pauline; Milleron, Olivier; Eliahou, Ludivine; Gross, Marie-Sylvie; Hanna, Nadine; Boileau, Catherine; Gouya, Laurent; Jondeau, Guillaume
- Abstract
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with considerable inter- and intra-familial clinical variability. The contribution of inherited modifiers to variability has not been quantified. We analyzed the distribution of 23 clinical features in 1306 well-phenotyped MFS patients carrying FBN1 mutations. We found strong correlations between features within the same system (i.e., ophthalmology vs. skeletal vs. cardiovascular) suggesting common underlying determinants, while features belonging to different systems were largely uncorrelated. We adapted a classical quantitative genetics model to estimate the heritability of each clinical feature from phenotypic correlations between relatives. Most clinical features showed strong familial aggregation and high heritability. We found a significant contribution by the major locus on the phenotypic variance only for ectopia lentis using a new strategy. Finally, we found evidence for the "Carter effect" in the MFS cardiovascular phenotype, which supports a polygenic model for MFS cardiovascular variability and indicates additional risk for children of MFS mothers with an aortic event. Our results demonstrate that an important part of the phenotypic variability in MFS is under the control of inherited modifiers, widely shared between features within the same system, but not among different systems. Further research must be performed to identify genetic modifiers of MFS severity.
- Subjects
MARFAN syndrome; GENETIC correlations; QUANTITATIVE genetics; MOTHER-child relationship; CONNECTIVE tissues; HERITABILITY; PATH analysis (Statistics)
- Publication
Genes, 2020, Vol 11, Issue 5, p574
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes11050574