Genetically Transmitted Eye Diseases

by Federico Bartolomei

Interview with Prof. Marco Seri of the Sant'Orsola-Malpighi Polyclinic.

It is possible to understand the importance of genetics in the development of diseases by considering estimates that indicate that in Europe 30 million people are diagnosed with a hereditary disease.
With the completion of the Human Genome Project, which allowed the complete codification of our DNA, today we are finally able to diagnose a greater number of genetically transmitted diseases:
"We can consider our DNA like an enormous book containing an impressive number of letters that shape the words of computed meaning which are our genes", explains Prof. Marco Seri, Director of the Operating Unit of Medical Genetics at Sant'Orsola-Malpighi Polyclinic: "it is now possible to read all these words and see if a letter has changed, indicating the appearance of a word without sense, which means if we are facing the mutation of a gene that determines the presence of a non-functional protein and, consequently, of a genetic disease. DNA also has variables that do not determine, in a direct manner, the presence of a disease, but that can, in conjunction with environmental factors, predispose a person to a disease."
As far as eye diseases are concerned, we know that a good number of them are transmitted genetically and can cause important disabilities: "among the genetic eyes diseases which can be transmitted to members of a family, we find some forms of corneal dystrophy, glaucoma, cataracts, retinal degeneration among which retinitis pigmentosa.
"Heterogeneous genetics", in other words the fact that the same disease can be caused by mutations in various genes, also exists. If we take, for example, retinitis pigmentosa, we know that more than 100 genes have been described and are responsible for the eye affections. Often, from a clinical point of view, patients cannot be distinguished between one another, but from the genetics point of view, their forms are different sometimes even with a different modality of transmission."

Image - The presence of a mutation in a gene of an individual's DNA determines the presence of a genetic disease. In the right part of the figure, it is possible to see how a mutation, present in heterozygous carriers, both parents who are first cousins, is transmitted from them to affected children who consequently end up homozygous carriers because of the mutation, and not to healthy children.

Picture - Dr. Claudio Graziano (left) and Prof. Marco Seri (right) at the Operational Unit of Medical Genetics of the Sant'Orsola-Malpighi Polyclinic where they are genetics consultant. Dr. Claudio Graziano is directly involved in genetics counselling specializing in inherited eye diseases.

Why would genetics counselling be important?
"There can be immediate effects on the individual as well as the family: it is possible to stabilize, for example, who are the healthy carriers of a disease and the risk to have a sick child if two healthy carriers of the same defect end up together."
What are future perspectives for genetic therapy?
"To know of an altered gene and consequently the protein that does not work could help understanding the mechanisms that cause the disease itself, that is its pathogenesis, and putting in place new therapeutic strategies, pharmacological or not.
Conceptually, genetic therapy would be a simple procedure based on modifying the altered gene in the cell affected by the disease.

In reality, it is a very complex process which application still today has remained isolated to a few cases."
At the present time, in Italy, experimentations are being conducted on a specific ocular pathology: "It is an experimentation for genetic therapy in patients with Leber's congenital amaurosis and a mutation of the gene RPE65, and it is lead by a team at the University of Naples and by the TIGEM lab in Naples as well. Data are very promising and we hope that in the future new experimentations will be carried out for other eye diseases."

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