scholarly journals Clinical and Genetic Correlations of Inherital Retinal Disease with Mutations in the ABCA4 Gene by Patients of the Russian Population

2021 ◽  
Vol 18 (4) ◽  
pp. 897-907
I. V. Zolnikova ◽  
V. V. Kadyshev ◽  
A. V. Marakhonov ◽  
A. B. Chernyak ◽  
S. V. Milash ◽  

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.

2018 ◽  
Suvi Mäkeläinen ◽  
Marta Gòdia ◽  
Minas Hellsand ◽  
Agnese Viluma ◽  
Daniela Hahn ◽  

Autosomal recessive retinal degenerative diseases cause visual impairment and blindness in humans and dogs. Currently, no standard treatment is available but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans. To study a novel form of retinal degeneration in Labrador retriever dogs with clinical signs indicating cone and rod degeneration, we used whole-genome sequencing of an affected sib-pair and their unaffected parents. A frameshift insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene (c.4176insC), leading to a premature stop codon in exon 28 (p.F1393Lfs1395) was identified. In contrast to unaffected dogs, no full-length ABCA4 protein was detected in the retina of an affected dog. The ABCA4 gene encodes a membrane transporter protein localized in the outer segments of rod and cone photoreceptors. In humans, the ABCA4 gene is associated with Stargardt disease (STGD), an autosomal recessive retinal degeneration leading to central visual impairment. A hallmark of STGD is the accumulation of lipofuscin deposits in the retinal pigment epithelium. The discovery of a canine homozygous ABCA4 loss-of-function mutation may advance the development of dog as a large animal model for human STGD.

Мария Альбертовна Елинсон ◽  
Ирина Васильевна Щербина

В статье рассматривается дифференциация субъектов Российской Федерации по величине прожиточного минимума в период с 2008 по 2018 гг. Произведена группировка субъектов РФ по уровню бедности населения. Применение методов статистического, картографического анализа позволило выявить концентрацию регионов в области низких значений, рост различий между богатыми и бедными регионами. The article considers the differentiation of the constituent entities of the Russian Federation in terms of minimum wage in the period from 2008 to 2018. The grouping of subjects of the country according to the level of poverty of the population is made. The application of statistical and cartographic analysis methods allowed us to identify the concentration of regions within low values, the growth of differences between rich and poor regions.

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 18-18
Leticia P Sanglard ◽  
Felipe Hickmann ◽  
Yijian Huang ◽  
Kent A Gray ◽  
Daniel Linhares ◽  

Abstract Immunoglobulin G antibody response, measured as sample-to-positive (S/P) ratio, to Porcine Reproductive and Respiratory Syndrome virus (PRRSV) has been proposed as an indicator trait for improved reproductive performance in PRRSV-infected purebred sows and PRRSV-vaccinated crossbred gilts. In this study, we investigated the genetic correlations (rg) of S/P ratio following a PRRSV outbreak and PRRSV-vaccination with performance in non-exposed and PRRSV-exposed sows. PRRSV outbreak phase was defined based on previously described methodologies after the detection of typical clinical signs of PRRSV infection. 541 Landrace sows had S/P ratio measured at ~54 days after the beginning of the PRRSV outbreak (S/Poutbreak), and 906 Landrace x Large White naïve F1 gilts had S/P ratio measured at ~50 days after vaccination with a commercial modified live PRRSV vaccine (S/PVx). 711 and 428 Landrace sows had reproductive performance recorded before and during the PRRSV outbreak, respectively. 811 vaccinated F1 animals had farrowing performance for up to 3 parities. All animals were genotyped for ~28K SNPs. The estimate of rg of S/Poutbreakwith S/PVx was high (rg±SE = 0.72±0.18). Estimates of rg of S/Poutbreak with reproductive performance in F1 sows were low to moderate, ranging from 0.05±0.23 (number stillborn) to 0.30±0.20 (total number born). Estimates of rg of S/PVxwith reproductive performance in non-infected purebred sows were moderate and favorable with number born alive (0.50±0.23), but low (0 to -0.11±0.23) with litter mortality traits. Estimates of rg of S/PVx were moderate and negative (-0.47±0.18) with the number of mummies in PRRSV-infected purebred sows and low with other traits (-0.29±0.18 for total number born to 0.05±0.18 for number stillborn). These results indicate that selection for antibody response following a PRRSV outbreak collected in purebred sows and to PRRSV vaccination collected in commercial crossbred gilts may increase litter size of non-infected and PRRSV-exposed purebred and commercial crossbred sows.

1987 ◽  
Vol 9 (1) ◽  
pp. 13-14
Frederick Hecht

Medical genetics is currently enjoying a time of exploration and discovery. Huntington disease has long been of interest in adult medicine. The onset of clinical signs and symptoms is usually delayed until midadulthood. It may seem strange in this context to focus on Huntington disease, but advances in molecular genetics have brought Huntington disease into the purview of pediatrics. These advances in molecular genetics make it possible to detect Huntington disease in a preclinical stage at or even before birth. The molecular approach does not replace prior approaches to Huntington disease but is synergistic and provides a model of the new genetics. Huntington disease is synonymous with Huntington chorea. It is named after George Huntington who, like his father and grandfather before him, studied the disease in families on Long Island, NY. Huntington disease is a more common hereditary disorder than phenylketonuria, which occurs in one of about 10,000 newborns in the United States. By contrast, about one in 2,000 persons is at risk for Huntington disease. Although most cases start clinically in midadulthood, usually between 35 and 42 years of age, there is great variability in age of onset. About 3% of cases are diagnosed as juvenile Huntington disease before the age of 15 years. Late onset is well known after 50 years of age.

2020 ◽  
Vol 21 (10) ◽  
pp. 3430
Aneta Ścieżyńska ◽  
Marta Soszyńska ◽  
Michał Komorowski ◽  
Anna Podgórska ◽  
Natalia Krześniak ◽  

ABCA4 gene mutations are the cause of a spectrum of ABCA4 retinopathies, and the most common juvenile macular degeneration is called Stargardt disease. ABCA4 has previously been observed almost exclusively in the retina. Therefore, studying the functional consequences of ABCA4 variants has required advanced molecular analysis techniques. The aim of the present study was to evaluate whether human hair follicles may be used for molecular analysis of the ABCA4 gene splice-site variants in patients with ABCA4 retinopathies. We assessed ABCA4 expression in hair follicles and skin at mRNA and protein levels by means of real-time PCR and Western blot analyses, respectively. We performed cDNA sequencing to reveal the presence of full-length ABCA4 transcripts and analyzed ABCA4 transcripts from three patients with Stargardt disease carrying different splice-site ABCA4 variants: c.5312+1G>A, c.5312+2T>G and c.5836-3C>A. cDNA analysis revealed that c.5312+1G>A, c.5312+2T>G variants led to the skipping of exon 37, and the c.5836-3C>A variant resulted in the insertion of 30 nucleotides into the transcript. Our results strongly argue for the use of hair follicles as a model for the molecular analysis of the pathogenicity of ABCA4 variants in patients with ABCA4 retinopathies.

2017 ◽  
Vol 60 (2) ◽  
pp. 140-147 ◽  
Inna V. Zolnikova ◽  
Vladimir V. Strelnikov ◽  
Natalia A. Skvortsova ◽  
Alexander S. Tanas ◽  
Debmalya Barh ◽  

2013 ◽  
Vol 71 (6) ◽  
pp. 645-651
Ibtissem Chouchene ◽  
Leila Largueche ◽  
Farah Ouechtati ◽  
Kawthar Derouiche ◽  
Ahmed Turki ◽  

2019 ◽  
Vol 10 ◽  
Fang-Yuan Hu ◽  
Jian-kang Li ◽  
Feng-Juan Gao ◽  
Yu-He Qi ◽  
Ping Xu ◽  

2018 ◽  
Vol 2018 ◽  
pp. 1-1
Smaragda Kamakari ◽  
Vassiliki Kokkinou ◽  
George Koutsodontis ◽  
Polixeni Stamatiou ◽  
Christoforos Giatzakis ◽  

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