Related Experiment Video

Updated: Jul 30, 2026

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

Marfan syndrome caused by a mutation in FBN1 that gives rise to cryptic splicing and a 33 nucleotide insertion in the

S Hutchinson1, B P Wordsworth, P A Handford

  • 1Department of Biochemistry, University of Oxford, OX1 3QU, UK.

Human Genetics
|November 10, 2001
PubMed

Insights

A novel splicing defect in the FBN1 gene causes Marfan syndrome. This study identifies a unique mutation leading to abnormal fibrillin-1 protein production, impacting connective tissue structure.

Area of Science:

  • Genetics
  • Molecular Biology
  • Biochemistry

Background:

  • Marfan syndrome is a genetic disorder affecting connective tissue, primarily caused by mutations in the FBN1 gene.
  • Fibrillin-1 is a crucial component of extracellular matrix microfibrils.
  • Diagnostic methods like heteroduplex analysis may not detect all FBN1 mutations.

Observation:

  • A patient with Marfan syndrome presented with a mutation undetectable by standard heteroduplex analysis.
  • Fibroblast cultures from the patient showed defective secretion of fibrillin-1 compared to controls.
  • Analysis revealed a 33-base pair insertion in the patient's FBN1 cDNA.

Findings:

  • The identified mutation involved a G+1-->A transversion in intron 46 of the FBN1 gene.
  • This intronic mutation activated a cryptic splice site, leading to an 11-amino acid insertion in epidermal growth factor-like domain 29 of fibrillin-1.
  • This represents the first reported instance of a splicing defect in FBN1 resulting in a full-length transcript with a significant amino acid insertion.

Implications:

  • This discovery expands the spectrum of FBN1 mutations associated with Marfan syndrome.
  • Understanding novel splicing defects is critical for accurate genetic diagnosis and counseling.
  • Further research into the functional consequences of this specific fibrillin-1 variant is warranted.

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

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene08:22

A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene

Published on: September 16, 2019

Related Concept Videos

Mutations01:39

Mutations

Overview
Translation01:31

Translation

Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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...