ArticleHuman molecular genetics2015
A microfibril assembly assay identifies different mechanisms of dominance underlying Marfan syndrome, stiff skin syndrome and acromelic dysplasias.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Pathogenic variants affecting the TB5 domain of the fibrillin-1 protein: not only in geleophysic/acromicric dysplasias but also in Marfan syndrome.Journal of medical genetics · 2024Article
- The fibrillinopathies: New insights with focus on the paradigm of opposing phenotypes for both FBN1 and FBN2.Human mutation · 2022Review
- Genotype-phenotype correlations of marfan syndrome and related fibrillinopathies: Phenomenon and molecular relevance.Frontiers in genetics · 2022Review
- POGLUT2 and POGLUT3 O-glucosylate multiple EGF repeats in fibrillin-1, -2, and LTBP1 and promote secretion of fibrillin-1.The Journal of biological chemistry · 2021Article
- Assembly assay identifies a critical region of human fibrillin-1 required for 10-12 nm diameter microfibril biogenesis.PloS one · 2021Article
- Cooperative Mechanism of ADAMTS/ ADAMTSL and Fibrillin-1 in the Marfan Syndrome and Acromelic Dysplasias.Frontiers in genetics · 2021Review
- Acromicric dysplasia with stiff skin syndrome-like severe cutaneous presentation in an 8-year-old boy with a missense FBN1 mutation: Case report and literature review.Molecular genetics & genomic medicine · 2020Review
- Limb- and tendon-specific Adamtsl2 deletion identifies a role for ADAMTSL2 in tendon growth in a mouse model for geleophysic dysplasia.Matrix biology : journal of the International Society for Matrix Biology · 2019Article
- Middle-Aged Female Diagnosed With Widespread Stiff Skin Syndrome.Archives of rheumatology · 2018Article
- Fell-Muir Lecture: Fibrillin microfibrils: structural tensometers of elastic tissues?International journal of experimental pathology · 2017Review
- Marfan syndrome: current perspectives.The application of clinical genetics · 2016Review
- Fibrillin-1 Regulates Skeletal Stem Cell Differentiation by Modulating TGFβ Activity Within the Marrow Niche.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- Fibrillin microfibrils in bone physiology.Matrix biology : journal of the International Society for Matrix BiologyReview
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Fibrillin-1 is the major component of the 10-12 nm diameter extracellular matrix microfibrils. The majority of mutations affecting the human fibrillin-1 gene, FBN1, result in Marfan syndrome (MFS), a common connective tissue disorder characterised by tall stature, ocular and cardiovascular defects. Recently, stiff skin syndrome (SSS) and a group of syndromes known collectively as the acromelic dysplasias, which typically result in short stature, skin thickening and joint stiffness, have been linked to FBN1 mutations that affect specific domains of the fibrillin-1 protein. Despite their apparent phenotypic differences, dysregulation of transforming growth factor β (TGFβ) is a common factor in all of these disorders. Using a newly developed assay to track the secretion and incorporation of full-length, GFP-tagged fibrillin-1 into the extracellular matrix, we investigated whether or not there were differences in the secretion and microfibril assembly profiles of fibrillin-1 variants containing substitutions associated with MFS, SSS or the acromelic dysplasias. We show that substitutions in fibrillin-1 domains TB4 and TB5 that cause SSS and the acromelic dysplasias do not prevent fibrillin-1 from being secreted or assembled into microfibrils, whereas MFS-associated substitutions in these domains result in a loss of recombinant protein in the culture medium and no association with microfibrils. These results suggest fundamental differences in the dominant pathogenic mechanisms underlying MFS, SSS and the acromelic dysplasias, which give rise to TGFβ dysregulation associated with these diseases.
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