Fibrinogen Mumbai: intracellular retention due to a novel G434D mutation in the Bbeta-chain gene

Related Experiment Video

Updated: Aug 8, 2026

Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
06:27

Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy

Published on: November 30, 2018

Luca Monaldini1, Rosanna Asselta, Stefano Duga

  • 1Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy. stefano.duga@unimi.it

Haematologica
|May 4, 2006
PubMed
Abstract

Insights

A novel G434D mutation in the fibrinogen Bbeta-chain gene causes severe hypofibrinogenemia by impairing fibrinogen secretion. This finding highlights the critical role of Bbeta-chain D domain folding in fibrinogen processing.

Area of Science:

  • Hematology
  • Molecular Genetics
  • Biochemistry

Background:

  • Afibrinogenemia and hypofibrinogenemia are rare inherited bleeding disorders.
  • Characterized by low plasma fibrinogen levels and variable bleeding severity.
  • 18 missense mutations are known, with 57 total mutations identified.

Observation:

  • A novel homozygous G-->A transition in exon 8 of the fibrinogen Bbeta-chain gene was identified in an Indian proband.
  • This resulted in a G434D missense mutation (fibrinogen Mumbai) in a conserved C-terminal D domain residue.
  • In vitro studies showed intracellular retention and reduced secretion of the mutant fibrinogen.

Findings:

  • The G434D substitution impairs fibrinogen secretion.
  • Intracellular retention of fibrinogen is a key mechanism.
  • This mutation leads to severe hypofibrinogenemia.

Implications:

  • Confirms the importance of Bbeta-chain D domain folding for proper intracellular fibrinogen processing.
  • Provides insight into the molecular mechanisms of hypofibrinogenemia.
  • Contributes to understanding rare inherited coagulation disorders.

More Related Videos

In Vivo Modeling of the Morbid Human Genome using Danio rerio12:31

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

Related Concept Videos

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...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
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...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...