Clinical polymorphism and genetic heterogeneity of isolated and syndromal forms of retinitis pigmentosa in closed isolates of the Republic of Buryatia

Background. Retinitis pigmentosa is a group of inherited degenerative retinal diseases resulting from the progressive death of cells of the pigment epithelium, photoreceptor cells - rods and then cones, which leads to gradual loss of vision.

Aim: to study the clinical polymorphism and genetic heterogeneity of isolated and syndromal forms of retinitis pigmentosa in closed isolates of the Republic of Buryatia.

Methods. The sample included 74 patients with a preliminary diagnosis of isolated retinitis pigmentosa or syndromal retinitis pigmentosa (Usher syndrome) according to the data of routine methods of research, living in closed isolates of the Republic of Buryatia. This report describes the structure of hereditary retinal pigment dystrophies in closed isolates of the Republic of Buryatia based on the data of clinical, instrumental (optical coherence tomography, electroretinography) and molecular genetic diagnostic methods (NGS, Sanger sequencing, MLPA).

Results. Among the examined group of population mutations were found in 13 genes with the highest frequency of mutations in USH2A (58,8%) and CHM (23,5%), NR2E3(17,6%) genes, with equal frequency of 11,8% in GUCY2D, SNRNP200, TULP1, CEP290 genes. ABCA4, GRK1, MY07A, PDE6A, RP1L1, TTC21B mutations were identified in one case (5.9%). In 64.7% of the identified mutations were pathogenic, in 17.6% were probably pathogenic and in another 17.6% were mutations with unknown clinical significance with possible relevance to the phenotype. Analyzing the quantitative distribution of patients according to certain types of inheritance, it was found that 83.4% of patients had autosomal recessive disease, 8.3% had autosomal dominant disease, and 8.3% had X-linked recessive disease. Changes in USH2A (Usherin) gene were verified in the majority of cases, in 10 out of 17 people who gave their consent for molecular genetic study, which, in its turn, allowed to establish the clinical and genetic diagnosis of Usher syndrome type 2A in 6 probands, isolated retinitis pigmentosa type 39 in 4 probands, including 3 patients with classic course of PR, 1 - with pigmentless form.

Conclusion. An interdisciplinary survey taking into account the data of clinical-instrumental and molecular genetic diagnostics allowed us to study the clinical polymorphism of a genetically heterogeneous group of retinal diseases among the Old Believers living in the territory of the Republic of Buryatia.

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