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Aim: to study genotype-phenotype correlations in patients with inherited retinal diseases with mutations in ABCA4 gene in Russian Federation.Patients and methods. 21 patients from Russian population aged from 7 to 51 years old (mean age 20 ± 11 years with best-corrected visual acuity from 0,02 to 0,6 (0,14 ± 0,11) with ABCA4-associated retinopathy, verified by molecular genetics methods. All patients besides standard ophthalmic examination and photodocumentation were performed Spectral-Domain OCT and fundus autofluorescence on Spectralis ®HRA+OCT (Heidelberg Engineering, Germany). Full-field electroretinogram (ERG), 30-Hz flicker ERG and macular chromatic ERG (MERG) to red stimulus were recorded on electroretinographic system MBN (MBN, Russia). (Russia) Molecular genetic studies were performed using Next Generation Sequencing (NGS) and Sandger direct sequencing. Results: In ABCA4-associated Stargardt disease 1 type (STGD1) genotype [p.L541P, p.A1038V] of «frequent» mutations was revealed in 9 patients, in 2 cases in was associated another “frequent” mutation p.G1961E. In 4 patients with genotype [p.L541P, p.A1038V] “severe” phenotype of Stargardt disease was found: with large defect of the ellipsoid zone and large zone of central reduced autofluorescence, severely subnormal macular ERG (MERG) to red stimulus and subnormal 30 Hz flicker and full-field maximal ERG. In one patient with these mutations in homozygous state ABCA4-associated cone-rod dystrophy (CORD3, clinically looking alike secondary retinal dystrophy is diagnosed. In 2 patients with genotype [p.L541P, p.A1038V] and mutation p.G1961E was found mild phenotype. One patient with homozygous mutation p.R653C autosomal recessive ABCA4-associated retinitis pigmentosa (RP19) was diagnosed. Clinical picture and autofluorescence were polymorphic in all patients.Conclusions. Our study with ophthalmological, molecular genetics and instrumental methods widens the spectrum of clinical signs of inherited eye diseases associated with mutations in АВСА4 gene, widens the spectrum mutations in Russian Federation and reveals clinicо-genetic genotype-phenotype correlations.

The purpose: to describe clinical cases of oculodental-digital dysplasia (ODDD, OMIM #164200) with mutation in GJA1 (OMIM 121014) with molecular genetic verification of the diagnosis.Methods. The article describes the clinical case of oculodental-digital dysplasia in a 51 years old patient. Patient underwent full ophthalmic examination including autorefractometry, visual acuity testing with full correction, tonometry, biomicroscopy, fundus examination and photo as well as kinetic perimetry, autofluorescence and optical coherence tomography (OCT) of macula and optic disk were performed. Electrophysiological examination included Visual Evoked Potentials (VEP) to flash and pattern stimulation, ISCEV standard electroretinograms (ERG) and macular ERG. For the verification of the diagnosis and pathologic gene molecular genetic examination was performed with family anamnesis previously attained.Results. The patient was complaining the deterioration of vision, hearing loss and the sense of smell. Visual deterioration was associated with nyctalopia. Natural history revealed glaucoma 2а which was diagnosed when he was 48 years old. Best corrected visual acuity was 1,0. Peripheral visual field defects were revealed bilaterally. High visual acuity correlated with normal foveal structure on OCTs the retinal nerve fiber layer (RNFL) was thinner than normal in temporal half; deep excavation was visualized in both eyes. Normal MERG and bilateral decrease of scotopic, maximal full-field ERG was recorded which correlated with nyctalopia, as well as subnormal photopic responses indicating cone system involvement. The genetics revealed characteristic features of the face: a small nose with hypoplasia of the wings of the nose, unfolded nostrils and a wide bridge of the nose (pseudohypertelorism). On right-wing the ear sink was detected 2 antitraguses. Changes fingers upper extremities — operated syndactyly IV and V on the background of brachydactyly of the fingers. On the legs on both sides — syndactyly III–IV. 10 years the sense of smell has been dereriorated. In the study of DNA in proband in direct Sanger sequencing of all exons 1–2 and regions of exon-intron compounds of gene GJA1, was found the pathogenic variant in second exon c.412G>A (p.Gly138Ser) in heterozygous state. Was established autosomal dominant type of disease.Conclusion. We are the first to describe rod-cone dystrophy in oculodental-digital dysplasia.