טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSafieh Christine
SubjectGenetic Characterisation of the Causes for Retinitis
Pigmentosa
DepartmentDepartment of Medicine
Supervisor Professor Tamar Ben-Yosef
Full Thesis textFull thesis text - English Version


Abstract

The composition of the Israeli population is very unique since it consists of a variety of ethnic groups. This variety is of utmost importance when it comes to genetic analysis. Each group has its own unique genetic makeup, which has been preserved through many years as a result of a secluded life pattern and inbreeding. Consequently, each group has its own specific disease-causing mutations.

 

RP is the most common form of Hereditary Retinal Degeneration (HRD). Patients initially suffer from night blindness, followed by loss of peripheral visual fields, an effect known as "Tunnel Vision" and at the final stages of the disease total blindness may occur.


RP is genetically heterogeneous. It can be inherited as autosomal recessive (AR), autosomal dominant (AD), or X-linked (XL). Mitochondrial (MT) and digenic patterns of inheritance have also been described. When RP appears as a single symptom, it is defined as "nonsyndromic RP". In other cases, RP is one of several symptoms of a certain genetic disease, then it is defined as "syndromic RP". One of the most common forms of syndromic RP is Usher syndrome (USH), which involves both RP and hearing loss.


Over 60 genes and loci have been implicated in RP, including twenty seven genes and 5 loci causing AR-nonsyndromic RP. Yet, in over 50% of the cases the underlying gene is still unknown.


In the current study, we aimed to find novel genes and mutations that cause RP, and by that improve the accuracy of diagnostic tools for retinal degeneration diseases such as RP. During our work we have found an unreported novel mutation in the MYO7A gene causing USH1B in a Bedouin Family. Moreover, we have found a novel gene, named C2ORF71, which causes nonsyndromic arRP in two unrelated Israeli Arab families and one Dutch family.  C2ORF71 is a mysterious novel gene with unknown functional domain and no homology to known gene. When we started characterizing it, we found that C2ORF71 is expressed almost solely in the retina in human body, and expressed starting from the embryonic period in the mouse eye. These results imply that C2ORF71 has an important role in the eye development and sight process. Such findings are of great importance to basic science and mainly to medicine, since they contribute to molecular diagnosis, carrier screening and genetic counseling in the relevant populations.