Study of genetics and design of the test-system for diagnosis of eye anterior chamber hereditary disorders: the case of congenital aniridia

Importance . Congenital malformations are the main cause of disability in infancy. Aniridia (OMIM #106210) is a severe autosomal dominant congenital disorder. Aniridia is mainly associated with pathogenic variants in the PAX6 gene. Objective . To investigate the mutational and clinical spectra of congenital aniridia in a cohort of Russian patients. To make a design of a protocol for diagnosis of congenital aniridia. Design, Setting and Participants. 34 patients with congenital aniridia from 27 unrelated families were analysed. DNA-diagnosis included sequencing of all coding exons of PAX6 gene as well as analysis of large 11p13 region deletions. Results . 22 sporadic and 12 familial cases of congenital aniridia patients underwent detailed ophthalmic examination and molecular diagnosis. Large 11p13 deletion affecting PAX6 and WT1 genes was identified in two patients, therefore they were diagnosed with WAGR syndrome. Molecular analysis involved Sanger sequencing of all PAX6 exons, as well as Multiplex Ligation-dependent Probe Amplification (MLPA), Loss Of Heterozygosity (LOH) assays and FISH analysis. Small intragenic mutations in PAX6 gene were identified in 23 patients including 7 novel and 8 different previously reported changes. Large deletions were found in the remaining 11 patients. This allowed designing the protocol for congenital aniridia diagnosis. Conclusions and Relevance . Mutation detection rate is 100% in the current study. The protocol for diagnosis of congenital aniridia was designed on the basis of genetic peculiarities in Russian aniridia patients.

наследственные заболевания, орган зрения, аниридия, WAGR синдром, тест-система, крупные хромосомные аберрации, вариации числа копий, FISH анализ, потеря гетерозиготности, мутации, medical genetics, hereditary diseases, the organ of vision, aniridia, WAGR syndrome, a test system, major chromosomal aberrations, copy number variations, FISH analysis, loss of heterozygosity analysis, mutations

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