GeneThe basic physical and functional units of heredity are the Genes. Genes are specific “coded” sequences bearing instructions on how to construct proteins. The proteins are the biological units that perform almost all life functions and are key components of the majority of the cellular structures. Although gene sequence modification is a natural process, some times these “code” changes can result in proteins unable to carry out its normal functions, a genetic disorder can result. Gene therapy is a technique for correcting defective genes responsible for disease development.

The recent advances in biology and medicine permitted to develop several strategies leading to the correction of abnormal genes. Most of the gene therapies studies inserts a normal gene into the genome to replace the "abnormal," disease-causing gene. The « normal » gene can be introduced on the patient’s body directly (in vivo gene therapy) or the defective gene is first corrected by a normal gene in cells (ex vivo gene therapy) from a donor (allogenic treatment) or from the same patient (autologous treatment).



What is EB

The term Epidermolysis Bullosa comprises a series of genetic disorders characterised by blistering skin conditions. The skin (epithelium) of people suffering of this disease is so fragile that even minor rasping could produce blistering. RDEB is caused by gene (Col7A1) mutations which lead either to an altered version of collagen VII, or a complete absence of the protein.



Figure 3: Scanning electron microscopy of Human Skin. © INSERM


The diverse clinical EB manifestations are grouped on three major EB types:


  1. EB simplex
  2. Junctional EB
  3. Dystrophic EB

The dominant and recessive types

EB is a genetic disorder with dominant and recessive forms. On the dominant form, the defective gene is inherited form only one parent who carries on his/her genetic information the malfunctioning gene. On the recessive form, both parents carry on and both inherit the defective gene to the child. The last possibility is that EB can be produced by a spontaneous mutation of the responsible gene during the gamete formation; both parents carry on the correct genetic information.  This genetic disorder touches equally both sexes.


The Dystrophic EB (DEB)

Dystrophic EB can be produced by a recessive or dominant condition. On this form, a single defective gene produces a non-functional Type VII Collagen protein, a filamentous protein. Under normal conditions, Type VII Collagen is a major component of filaments anchoring the epidermis (upper layer of the skin) with the dermis (lower layer).


Recessive DEB Symptoms

A fragile skin that blisters easily can produce serious clinical complications (i.e. infections). On the middle forms of DEB the affected regions can be restricted to the hands, feet, elbows and knees. Nails have a deformed shape. Soft tissues, like the oesophagus can also be affected. Severe recessive forms can affect large body surfaces; nail modification or loss, itching, atrophic scarring, anaemia and growth retardation. Cases of eye inflammation with erosion of the cornea, loss of teeth and blistering of the alimentary tract have also been reported.