TRASMISSION OF THE HEREDITARY ANGIOEDEMA

Hereditary angioedema is a family disorder that is transmitted by a parent to his child, due to a genetic mutation located in a chromosome.

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HEREDITARY TRANSMISSION OF THE DISORDER:

INTRODUCTION

The genetic patrimony of each individual consists of: 46 chromosomes

• 23 inherited from the father
  
• 23 inherited from the mother
  

Each chromosome consists of numerous genes, each of which contains the necessary information needed for the production of a single protien.

Since in each individual every chromosome is present in 2 copies, we own 2 copies of each gene: one derives from the father and one from the mother.

The C1 inhibitor, like all proteins, is also codified from it's copies of genes: one from paternal and one from maternal origins.

It is sufficient that only one of the 2 genes for the C1 inhibitor contains an error (what is called a mutation) in order to have this disorder.

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TRANSMISSION OF THE DISORDER

• Sick Gene: Gene Malato
  
• Parents: Genitori
  
• Germinal cells: Cellule Germinali
  
• Zygote: Zigote
  

Only the child that inherited the mutated gene from one of his parent's has the disorder and can transmit it to his descendants.

The child that inherits from his parents both good genes does not have the disorder and therefore the transmission to the next generation ends.

• A person can have the disorder when the parents are healthy.
  
• In this case during the formation of the germinal cells in one of the 2 parents a spontaneous mutation happened in one of the 2 C1 inhibitor genes.
  
• Heathly parent: genitore sano
• Germinal cells: Cellule germinali

• Heathly parents: genitore sano
  
• Germinal cells: Cellule germinali
  
• Zygote: Zigote

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EFFECTS OF THE MUTATIONS

Depending on the type, the dimension and the location of the mutation inside the gene we can have different effects of C1 inhibitor :

• The protein does not get reproduced at all
  
• Produces a protein with an altered structure
  

TRIDIMENSIONAL STRUCTURE OF C1 INHIBITOR

THE PROTEIN WITH ALTERED STRUCTURE:

• Can be immediately destroyed by the same cell that produced it.
  
• Can be completely incapable to perform
  
• Can interfere with other systems

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MUTATION RESEARCH IN 154 ITALIAN FAMILIES CARRIERS OF HEREDITARY ANGIOEDEMA

To date our group has identified the mutation of the gene in 55 families.

47 different mutations were identified.

A more thorough study of the effects of some particular types of mutations of the C1 inhibitor gene is necessary for a better comprehension of the mechanism responsible for the onset of angioedema.

THE PROTEOMA

Is a new technique which at the moment is being used, which permits a simultaneous study of proteins present in a cell. The goal is to discover the eventual interference's of the mutated protein with other systems.