Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes

Related Experiment Video

Updated: Aug 17, 2026

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

B Lee1, M Godfrey, E Vitale

  • 1Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029.

Nature
|July 25, 1991
PubMed

Insights

Researchers identified mutations in the fibrillin gene as a likely cause for Marfan syndrome (MFS) and related connective tissue disorders. This finding links specific genetic defects to distinct MFS phenotypes, improving diagnostic understanding.

Area of Science:

  • Genetics
  • Molecular Biology
  • Connective Tissue Disorders

Background:

  • Marfan syndrome (MFS) is a common genetic disorder affecting connective tissue, leading to skeletal, cardiovascular, and ocular issues.
  • Current MFS diagnosis relies on clinical criteria as the underlying genetic defect remains unknown.
  • Cardiovascular complications significantly reduce life expectancy in MFS patients.

Purpose of the Study:

  • To identify the genetic basis of Marfan syndrome and related connective tissue disorders.
  • To investigate the role of fibrillin in the etiology of MFS.
  • To differentiate between genetically distinct conditions sharing MFS-like features.

Main Methods:

  • Immunohistochemical studies implicating fibrillin in MFS.
  • Genetic linkage analysis using random probes to localize the MFS locus.
  • Cloning and mapping of fibrillin genes to specific chromosomal locations (15q15-21 and 5q23-31).

Main Results:

  • The fibrillin gene was cloned, mapped to chromosome 15q15-21, and linked to Marfan syndrome.
  • A second, related fibrillin gene was identified and mapped to chromosome 5q23-31.
  • This second gene was linked to congenital contractural arachnodactyly, a condition with overlapping features with MFS.

Conclusions:

  • The identification and mapping of two fibrillin genes provide a genetic explanation for Marfan syndrome and related phenotypes.
  • Cosegregation of fibrillin genes with distinct syndromes suggests mutations in these genes are responsible for different MFS phenotypes.
  • This research advances the understanding of connective tissue disorders and their genetic underpinnings.

More Related Videos

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Biological Preparation and Mechanical Technique for Determining Viscoelastic Properties of Zonular Fibers06:39

Biological Preparation and Mechanical Technique for Determining Viscoelastic Properties of Zonular Fibers

Published on: December 16, 2021

Related Concept Videos

Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
Sex-linked Disorders01:43

Sex-linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
Fibril-associated Collagen01:11

Fibril-associated Collagen

Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
Type IV Collagen of Basal Lamina01:05

Type IV Collagen of Basal Lamina

Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen  forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.
A type IV collagen molecule has six alpha chains which can exist in...
Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...