Fibrillin protein pleiotropy: Acromelic dysplasias

Lynn Sakai, Douglas R. Keene

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The fibrillins are large extracellular matrix molecules that polymerize to form microfibrils. Fibrillin microfibrils are distinctive architectural elements that are both ubiquitous in the connective tissue space and also unique, displaying tissue-specific patterns. Mutations in the genes for fibrillin-1 (FBN1) result in multiple distinct pleiotropic disorders. Most of the more than 3000 mutations known today in FBN1 cause the Marfan syndrome. Marfan mutations can occur in any of the 56 domains that compose fibrillin-1. In contrast, rare mutations in FBN1 that are confined to only certain domains cause several different types of acromelic dysplasia. These genetic disorders demonstrate that specific domains of fibrillin-1 perform roles important to musculoskeletal growth. Many of the phenotypes of acromelic dysplasias are the opposite of those found in Marfan syndrome. Knowledge of the functions and structural organization of fibrillin molecules within microfibrils is required to understand how one protein and one gene can be the basis for multiple genetic disorders.

Original languageEnglish (US)
JournalMatrix Biology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Microfibrils
Marfan Syndrome
Mutation
Inborn Genetic Diseases
Proteins
Connective Tissue
Extracellular Matrix
Fibrillin-1
Fibrillins
Phenotype
Growth
Genes

Keywords

  • Acromicric dysplasia
  • Fibrillin
  • Geleophysic dysplasia
  • Stiff Skin Syndrome
  • Weill-Marchesani syndrome

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Fibrillin protein pleiotropy : Acromelic dysplasias. / Sakai, Lynn; Keene, Douglas R.

In: Matrix Biology, 01.01.2018.

Research output: Contribution to journalArticle

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