„Towards the light: unraveling genetic basis of hereditary retinal diseases in Poland”
(acronym: RETINA)

Project supported by the National Science Centre, Poland under the „SONATA 10” programme

Total cost: 871 192,00 PLN
Centre Contribution: 639 320,00 PLN
Duration: 7/11/2016 – 6/11/2018

Principal Investigator: dr Anna Tracewska
Project Consortium:

  1. Wrocławskie Centrum Badań EIT+ sp. z o. o. – Lider Konsorcjum
  2. Instytut „Pomnik – Centrum Zdrowia Dziecka”
  3. Warszawski Uniwersytet Medyczny

Hereditary retinal diseases (HRD) are congenital disorders resulting in a significant deterioration of vision, and often lead to complete blindness. They involve almost all modes of inheritance, from autosomal dominant and recessive to X-linked inheritance pattern. According to the European Commission, due to the prevalence of less than 1/2000 individuals, HRD belong to the group of rare diseases. At the moment, mutations in 125 genes are described in non-syndromic hereditary retinal diseases; it is estimated that the changes in these genes explain 80% of HRD. So far, the genetic diagnostics of these diseases in Poland was very expensive and inefficient, because existing panels containing hundreds of mutations have been developed based on studies conducted in Western populations. The effectiveness of such analyses in the Netherlands has been assessed at 15%. Carefully estimating, the effectiveness of this method in the Polish population is likely a couple of times lower, due to genetic diversity and highly probable presence of other founder mutations in the region. Retinal degenerative diseases require various diagnostic approaches dependent on the frequency of a particular type of mutation or involvement of a particular gene. For example, until recently in the Netherlands in Leber congenital amaurosis patients, first variant to be analysed was intronic mutation of the CEP290 gene; in France, patients with retinitis pigmentosa were initially tested for the coding part of EYS. Due to enormous heterogeneity of HRD and the resulting high analysis costs, the frequency of mutations in genes involved in these diseases in Poland is not known. Obtaining a genetic diagnosis is important from the perspective of a patient due to gaining the knowledge about the inheritance type of the disease and emerging treatment options. This project aims to evaluate the profile of genetic mutations in 108 known genes involved in hereditary retinal diseases, which in the future will enable developing inexpensive and effective diagnostic method. Statistically, approximately 20% of patients suffer from retinal disorders of unknown cause. In a subgroup of patients in whom we will not be able to detect causative mutations, we plan to search for novel genes involved in these diseases using next generation sequencing of the coding parts of all genes present in the human genome (i.e. exome sequencing).