The spectrum of mutations in the patients presenting with ABCA4-associated Stargardt's disease in a Russian population

Abstract

Introduction. Stargardt's disease is a hereditary retinal dystrophy characterized by the early manifestation and the progressive deterioration of visual acuity. The spectrum of mutations in the ABCA4 gene associated with this pathology in the Russian Federation has not been fully investigated. Aim. The objective of the present study was to elucidate the spectrum of mutations in the ABCA4 gene in the Russian patients presenting Stargardt's disease. Materials and methods. The study included a total of 38 unrelated patients at the age varying from 6 to 48 (mean 20 ± 8.9) years having the clinically confirmed diagnosis of Stargardt's disease. The search of mutations in DNA extracted from the peripheral blood lymphocytes of the patients was carried out with the use of a set of oligonucleotide primers (Ion Ampliseq Inherited Disease Panel; Life Technologies, USA). The Ion Torrent PGM Sequencer (Life Technologies, USA) was used for the parallel semiconductor sequencing of the gene-coding regions. All the patients underwent the standard ophthalmological examination, electroretinography, optical coherence tomography, and fundus autofluorescence. Results. We established the spectrum of mutations in the ABCA4 gene in the patients of a Russian population suffering from autosomal-recessive Stargardt's disease. We identified 45 alleles responsible for the development of this condition. 14 of them had been earlier described in the Russian patients while 19 were discovered for the first time in this country although they had been known to occur in other populations. Moreover, we described 12 novel heterozygous variations, viz. c.230T>A (rs61748527), c.4956T>G (rs61750561), c.2820>G (rs81749445). c.5226delT, c.2537A>T, c.57353T, c.893delG, c.702 insATC, c.3896T>G, c.1356delA, c.1341delGAT, and c.231insGAAAA. Discussion. The study has revealed the rather variable phenotype in the patients presenting with ABCA4-associated Stargardt's disease. A wide variety of mutations were shown to be responsible for the difference of the clinical picture of this condition in individual patients. The comparison of the genotypes and the phenotypes has demonstrated the differential effect of the concrete mutations. Conclusion. The spectrum of mutations in the patients presenting with ABCA4-associated Stargardt's disease in the surveyed Russian population is different from that in other populations. We have revealed 12 previously unknown mutations; moreover 19 mutations have been described for the first time in this country although they had been previously known to occur in other populations.