| Autor: |
Peeters, Silke, De Kinderen, Pauline, Meester, Josephina A. N., Verstraeten, Aline, Loeys, Bart L. |
| Zdroj: |
Human Mutation; Jul2022, Vol. 43 Issue 7, p815-831, 17p |
| Abstrakt: |
Different pathogenic variants in the fibrillin‐1 gene (FBN1) cause Marfan syndrome and acromelic dysplasias. Whereas the musculoskeletal features of Marfan syndrome involve tall stature, arachnodactyly, joint hypermobility, and muscle hypoplasia, acromelic dysplasia patients present with short stature, brachydactyly, stiff joints, and hypermuscularity. Similarly, pathogenic variants in the fibrillin‐2 gene (FBN2) cause either a Marfanoid congenital contractural arachnodactyly or a FBN2‐related acromelic dysplasia that most prominently presents with brachydactyly. The phenotypic and molecular resemblances between both the FBN1 and FBN2‐related disorders suggest that reciprocal pathomechanistic lessons can be learned. In this review, we provide an updated overview and comparison of the phenotypic and mutational spectra of both the "tall" and "short" fibrillinopathies. The future parallel functional study of both FBN1/2‐related disorders will reveal new insights into how pathogenic fibrillin variants differently affect the fibrillin microfibril network and/or growth factor homeostasis in clinically opposite syndromes. This knowledge may eventually be translated into new therapeutic approaches by targeting or modulating the fibrillin microfibril network and/or the signaling pathways under its control. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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