Hereditary Eye Diseases Research Articles

Interexaminer agreement of gonioscopy examinations in dogs using the European College of Veterinary Ophthalmologists Hereditary Eye Diseases grading scheme.

Prospective observational study with preregistered study protocol to assess interexaminer agreement using the 2022 European College of Veterinary Ophthalmologists Hereditary Eye Disease (ECVO-HED) gonioscopy grading scheme. Sixty client-owned dogs presented for gonioscopy as part of the required certification process prior to breeding. Two ECVO diplomates with comparable clinical experience performed gonioscopy with a Koeppe gonioscopy lens and slit-lamp biomicroscope at 10x magnification on all eyes in a randomized fashion. One hundred and eighteen of 120 eyes (60 dogs) were included. In 110/118 eyes (93%), both examiners provided the same breeding recommendation (yes/no). This translated into an agreement on the final breeding recommendation in 58/60 dogs (97%). Examiners disagreed on pectinate ligament abnormality (PLA) grading in 19/118 eyes and iridocorneal angle width (ICAW) grading in 9/118 eyes. PLA grading disagreement was mostly observed between neighboring grades. Disagreement between PLA and ICAW grading sometimes occurred within the same eye accounting for an observed disagreement in iridocorneal angle abnormality (ICAA) grading in 19/118 eyes in total. Cohen's kappa was Κ = 0.62 (95% TI 0.34-0.89), whereas maximum kappa was maxΚ = 0.82 (95% TI 0.59-1). Mixed model analysis suggested no significant examiner influence on breeding recommendations (OR 0.17; 95% CI 0.02-1.12, p = .09). Although examiners disagreed on ICAA grading in 19/118 eyes, this resulted in a different breeding recommendation (yes/no) in eight eyes and in two dogs only. Therefore, the use of the 2022 ECVO-HED gonioscopy grading scheme seems to result in examiners providing the same breeding recommendations in most cases.

Seeing in Color: Inclusion and Characterization of Hereditary Eye Disease in African Americans.

Hereditary eye diseases (HEDs) are individually rare but affect millions globally. The era of molecular genetics has ushered major advances in the study of these disorders; however, the inclusivity and population diversity of this research is unknown. Questions on the accuracy and applicability of these findings in diverse populations, especially African American patients, came up consistently during counselling sessions. This also raised the possibility of missed opportunities for broader understanding of these rare diseases. We conducted a literature review to measure the representation of African Americans in genomic research surrounding nine HEDs. A detailed literature search using a predetermined set of search terms for each of nine HED categories was performed across PubMed, Embase, Web of Science, and Scopus focusing on studies published between Jan 1990 and July 2021. Predetermined inclusion criteria were applied to filter the sources. We identified 46 studies clearly reporting HED characterization in African Americans. Analysis of these inclusive studies revealed unique findings demonstrating the known usefulness of including diverse cohorts in genomics research. HED characterization in diverse participants, specifically African Americans, is identified as a knowledge gap area. Genomic research is more applicable to patients when conducted in populations that share their ancestral background. Greater inclusion of African Americans in ophthalmic genetics research is a scientific imperative and a needed step in the pursuit of the best possible patient care for populations of all ancestries. This work reveals gaps in genomic research in African Americans with HEDs.

Application of whole exome sequencing technology in the diagnosis of hereditary eye diseases

Objective: To evaluate the application of whole exome sequencing (WES) in the diagnosis of hereditary eye diseases. Methods: A total of 24 patients who came to the Obstetrics and Gynecology Hospital of Fudan University for reproductive genetic counseling from December 2020 to December 2023 with the main complaint of congenital eye disorders were included in this study. All cases had no known infections or exposure to known teratogenic drugs, karyotype and chromosome microarray analysis (CMA) abnormalities. Genomic DNA was extracted from the peripheral blood of the probands and their family members and tested for WES. Among them, three individual WES and 21 Trio WES were performed. Potential pathogenic sites were screened and analyzed by Sanger sequencing. For RPGRIP1:c.1611+26G>A site, minigene vector was constructed and RT-qPCR was performed to detect the effect of mRNA splicing. Results: A total of 24 families were collected in this study, of which 20 yielded positive results, achieving a diagnosis rate of 83.3% (20/24). The results involved 21 genes and identified 30 distinct variants, 19 of which were new variants reported. Prenatal diagnostic analysis of family 3 revealed that the fetus carried a c.6970G>T heterozygous nonsense mutation in the PRPF8 gene. The results of RT-PCR with the minigene vector at the non-classical splice site in family 24 indicated that the transcription product of the mutant plasmid was partially retained 104 bp in intron 12, resulting in a p.Glu538Valfs*12 alteration of the protein. Conclusions: The high detection rate of WES in the diagnosis of hereditary eye diseases further supports the advantages of its application as an important molecular detection tool for determining the etiology of hereditary eye diseases.

Experience in managing patients with X-linked congenital retinoschisis

AIM: To describe the clinical manifestations and management experience of patients with X-linked congenital retinoschisis (XLRS).
 MATERIAL AND METHODS: The study was conducted in the ophthalmology department of the multidisciplinary clinical medical center Bonum (Yekaterinburg). Two brothers with XLRS were under observation. They underwent complete ophthalmological examinations, including electrophysiological examinations, optical coherence tomography (OCT), and fundus photoregistration. The mother refused genetic testing.
 RESULTS: Both siblings had early (up to 1 year) manifestations of central foveolamellar and peripheral bullous retinoschisis. The parents are phenotypically healthy, and the relatives have no hereditary eye diseases. The younger brother had a progressive peripheral retinoschisis and underwent barrier laser retinopexy; as a result, the progression stopped at the last examination. Acetazolamide 125 mg given orally daily for 4 weeks did not have a noticeable effect on the volume of bullous cavities. The older brother had been under observation for 4 years, and spontaneous closure of retinal cavities on the periphery in one eye and retinal detachment in the other after surgical treatment of retinoschisis were observed.
 CONCLUSION: Clinical cases of long-term follow-up of two brothers with XLRS are described. OCT is indicated to diagnose, assess the length and the state of the vitreoretinal interface, and monitor XLRS. Electroretignography is a specific and sensitive method for the complex diagnosis of XLRS. Barrier laser retinopexy is indicated for progressive peripheral retinoschisis. The efficacy and safety of carbonic anhydrase inhibitors in patients with XLRS require further study.

Морфологические особенности макулы у детей

With the development of modern technologies, diagnosing genetic diseases is not very difficult. The main difficulty is the assumption of the presence of a mutation when there are no ophthalmoscopic signs or functional disorders. Fundamental research into the morphology of the posterior pole of the eyeball in children has serious applied significance. Detection of the disease in the early stages allows young patients to receive high-quality and timely treatment, maintaining a high quality of life. Purpose of the study: to identify the morphological features of the macula in children. A retrospective analysis of optical coherence tomography materials was carried out on 24 children aged 4 to 12 years (average age 9.1 ± 2.5 years). All children had high visual functions; there were no hereditary eye diseases in their parents or family. The study was carried out on an Optovue RTVue XR Avanti Sistem device using standard Retina Map and 3D Retina programs. Conclusions: Intravital anatomy of the posterior pole of the eyeball can be qualitatively and quantitatively described using optical coherence tomography. With increasing age, the thickness of the retina in the central zone of the macula increases, and in the area of the retinal eminence decreases. The anatomical shape of the macula area does not change throughout childhood. Keywords: macula, human anatomy, age characteristics, individual approach

Deciphering a crucial dimeric interface governing Norrin dimerization and the pathogenesis of familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disease that could cause blindness. It has been established that Norrin forms dimers to activate β-catenin signaling, yet the core interface for Norrin dimerization and the precise mechanism by which Norrin dimerization contributes to the pathogenesis of FEVR remain elusive. Here, we report an NDP variant, c.265T>C (p.Phe89Leu), that interrupted β-catenin signaling by disrupting Norrin dimerization. Structural and functional analysis revealed that the Phe-89 of one Norrin monomer interacts with Pro-98, Ser-101, Arg-121, and Ile-123 of another, forming two core symmetrical dimerization interfaces that are pivotal for the formation of a "hand-by-arm" dimer. Intriguingly, we proved that one of the two core symmetrical interfaces is sufficient for dimerization and activation of β-catenin signaling, with a substantial contribution from the Phe-89/Pro-98 interaction. Further functional analysis revealed that the disruption of both dimeric interfaces eliminates potential binding sites for LRP5, which could be partially restored by over-expression of TSPAN12. In conclusion, our findings unveil a core dimerization interface that regulates Norrin/LRP5 interaction, highlighting the essential role of Norrin dimerization on β-catenin signaling and providing potential therapeutic avenues for the treatment of FEVR.

Longitudinal changes of refractive error in preschool children with congenital ectopia lentis.

Congenital ectopia lentis (CEL) is a hereditary eye disease which severely impacts preschool children's visual function and development. This study aimed to evaluate the longitudinal changes in spherical equivalent (SE) refractive error in preschool children with CEL. A retrospective cohort study was conducted at Zhongshan Ophthalmic Center, Guangzhou, China. Medical records of CEL patients under 6-year-old who were diagnosed with Marfan syndrome at the initial visit from January 2014 to March 2022 were collected and were divided into surgery and non-surgery groups. Mean change rate of SE in the two groups was evaluated, and the potential associated factors of SE change rate were investigated by mixed-effect regression model. A total of 94 preschool patients from 14 provinces of China were included. Among the 42 children of the surgery group, the mean age with standard deviation (SD) was 5.02 ± 0.81years and patients experienced a myopic shift of -0.05 ± 0.09D/month in average. The mean age with SD of the 52 children of the non-surgery group was 4.34 ± 1.02years, and the mean myopic shift was -0.09 ± 0.14D/month. The mixed-effect regression model identified that higher degree of myopia at baseline was associated with slower myopic shift both in surgery (β = 0.901, 95% CI: 0.822 ~ 0.980, P < 0.001) and in non-surgery group (β = 1.006, 95% CI: 0.977 ~ 1.034, P < 0.001) in CEL patients. Surgical treatment (β = 2.635, 95% CI: 1.376 ~ 3.894, P < 0.001) was associated with slower myopic shift in all participants CEL patients. Myopic progression was slower in the surgery group than in the non-surgery group of CEL. Preschool CEL patients who met the surgical indication are suggested being performed with timely surgery to slow down the myopic progression.

Screening copy number variations in 35 unsolved inherited retinal disease families

The purpose of this study was to screen Copy Number Variations (CNVs) in 35 unsolved Inherited Retinal Dystrophy (IRD) families. Initially, next generation sequencing, including a specific Hereditary Eye Disease Enrichment Panel or Whole exome sequencing, was employed to screen (likely) pathogenic Single-nucleotide Variants (SNVs) and small Insertions and Deletions (indels) for these cases. All available SNVs and indels were further validated and co-segregation analyses were performed in available family members by Sanger sequencing. If not, after excluding deep intronic variants, Multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescence PCR (QF-PCR) and Sanger sequencing were employed to screen CNVs. We determined that 18 probands who had heterozygous SNVs/indels or whose parents were not consanguineous but had homozygous SNVs/indels in autosomal recessive IRDs genes had CNVs in another allele of these genes, 11 families had disease-causing hemizygous CNVs in X-linked IRD genes, 6 families had (likely) pathogenic heterozygous CNVs in PRPF31 gene. Of 35 families, 33 different CNVs in 16 IRD-associated genes were detected, with PRPF31, EYS and USH2A the most common disease-causing gene in CNVs. Twenty-six and 7 of them were deletion and duplication CNVs, respectively. Among them, 14 CNVs were first reported in this study. Our research indicates that CNVs contribute a lot to IRDs, and screening of CNVs substantially increases the diagnostic rate of IRD. Our results emphasize that MLPA and QF-PCR are ideal methods to validate CNVs, and the novel CNVs reported herein expand the mutational spectrums of IRDs.

Topical issues in pediatric ophthalmogenetics: diversity and prevalence of hereditary eye pathology

According to the World Health Organization, hereditary eye pathologies (HEP) constitute a significant proportion of ophthalmologic diseases (at least 35% in total and up to 40%in children), resulting in substantial disability (65-70%). However, there is a lack of data on the prevalence and diversity of HEP in the Russian Federation. Therefore, it is crucial to study the prevalence and etiological nature of these diseases using modern genome technologies, in order to identify frequent forms, enable early detection in children, and develop effective therapeutic and preventive measures. Objective: The objective of this study was to estimate the prevalence of HEP in children, both as isolated conditions and as part of hereditary diseases and syndromes, in seven regions of the Russian Federation, while identifying frequently occurring nosological forms. Materials and methods: An epidemiological and clinical genetic study was conducted in 60 districts across the regions of Rostov, Kirov, Republics of Chuvashia, Udmurtia, Bashkortostan, Tatarstan, and Karachay-Cherkessia, encompassing a total population of 2,434,460 individuals, including 480,575 children. The study encompassed the entire population of the selected areas, regardless of age, and followed an original protocol for genetic and epidemiological research established at the Laboratory of Genetic Epidemiology. The methods employed included clinical-genetic, genealogical, clinical-laboratory, and molecular-genetic techniques, such as full-exome sequencing. The prevalence of visual organ diseases was calculated. Results: The results revealed a total of 449 patients with 56 different forms of isolated hereditary eye pathology (IHEP), indicating a prevalence of 1:1070 children. Additionally, 507 pediatric patients were identified with eye involvement as a symptom of 50 hereditary diseases and syndromes (SHEP), resulting in a prevalence of 1:954 children. Overall, hereditary eye lesions affecting various eye structures were identified in 956 pediatric patients, yielding a prevalence of 1:504 children. Frequent nosological forms were identified for both disease groups: 17 in IHEP and 14 in SHEP. Notably, these frequent hereditary eye diseases accounted for more than 80% of all identified patients with hereditary pathology (83.30% and 88.10% for IHEP and SHEP, respectively). Conclusion: This study provides new insights into the epidemiology of hereditary eye pathologies in the Russian Federation and describes frequent diseases within this population. These findings will contribute to improving research and clinical practices, expanding the range of treatable conditions, and informing targeted programs and measures in the field of children’s healthcare.

Novel mutations of the X-linked genes associated with early-onset high myopia in five Chinese families

PurposeTo report novel pathogenic variants of X-linked genes in five Chinese families with early-onset high myopia (eoHM) by using whole-exome sequencing and analyzing the phenotypic features.Methods5 probands with X-linked recessive related eoHM were collected in Ningxia Eye Hospital from January 2021 to June 2022. The probands and their family members received comprehensive ophthalmic examinations,and DNA was abstracted from patients and family members. Whole-exome sequencing was performed on probands to screen the causative variants, and all suspected pathogenic variants were determined by Sanger sequencing and co-segregation analysis was performed on available family members. The pathogenicity of novel variants was predicted using silico analysis and evaluated according to ACMG guidelines. RT-qPCR was used to detect differences in the relative mRNAs expression of candidate gene in mRNAs available with the proband and family members in the pedigree 2. The relationship between genetic variants and clinical features was analyzed.ResultsAll probands were male, and all pedigrees conformed to an X-linked recessive inheritance pattern. They were diagnosed with high myopia at their first visits between 4 and 7 years old. Spherical equivalent ranged between − 6.00D and − 11.00D.The five novel hemizygous variants were found in the probands, containing frameshift deletion variant c.797_801del (p.Val266Alafs*75) of OPN1LW gene in the pedigree 1, nonsense variant c.513G > A (p.Trp171Ter)of RP2 gene in the pedigree 2, missense variant c.98G > T (p.Cys33Phe) of GPR143 gene in the pedigree 3, frameshift deletion variant c.1876_1877del (p.Met626Valfs*22) of FRMD7 gene in the pedigree 4 and inframe deletion variant c.670_ 675del (p.Glu192_ Glu193del) of HMGB3 gene in the pedigree 5. All variants were classified as pathogenic or likely pathogenic by the interpretation principles of HGMD sequence variants and ACMG guidelines. In family 2, RT-qPCR showed that the mRNA expression of RP2 gene was lower in the proband than in other normal family members, indicating that such variant caused an effect on gene function at the mRNA expression level. Further clinical examination showed that pedigrees 1, 2, 3, and 4 were diagnosed as X-linked recessive hereditary eye disease with early-onset high myopia, including quiescent cone dysfunction, retinitis pigmentosa, ocular albinism, and idiopathic congenital nystagmus respectively. The pedigree 5 had eoHM in the right eye and ptosis in both eyes.ConclusionIn this paper,we are the first to report five novel hemizygous variants in OPN1LW, RP2, GPR143, FRMD7, HMGB3 genes are associated with eoHM. Our study extends the genotypic spectrums for eoHM and better assists ophthalmologists in assessing, diagnosing, and conducting genetic screening for eoHM.

Genetic counselling and gene analysis in patients with hereditary ocular diseases

Purpose. Non-syndromic hereditary ocular diseases can lead to severe functional limitations of vision at all ages. Therefore, molecular genetic research into the causes of hereditary ocular diseases is of paramount importance. Due to the increasingly optimised pathophysiologically adapted treatments and gene therapy options, a rapid determination of the genetic cause of hereditary ocular diseases is neces- sary, also to increase the chances of treatment at early stages of the disease. In this context, the authors retrospectively analysed the database of the “rare diseases” consultation hour of the PraxisKlinik Augenärzte Halle, which has been in existence since 2016, for patients with a suspected hereditary ophthalmological disease after molecular genetic diagnostics, counselling and therapy options. Material and Methods. 367 index patients were treated dur- ing the period under consideration. In 221 (60.2 %) of them, the molecular genetic cause of the underlying disease could be found. In addition to a large group of patients with cor- neal dystrophies (304 patients, detection rate 61.2 %), we treated 23 index patients with hereditary retinal diseases (detection rate 69.6 %), 28 index patients with complex mal- formations (detection rate 50 %) and 15 index patients with optic atrophies (detection rate 33.4 %). In addition to the ophthalmological-clinical examination and diagnostics, ge- nealogical analysis and molecular genetic testing were always performed. Results. On the basis of 3 case studies with a molecularly ge- netically proven hereditary retinal disease (X-linked recessive inherited juvenile retinoschisis, hemizygous missense muta- tion in the RS1 gene; enhanced S-Cone syndrome, compound heterozygous mutation in the RS2E3 gene; oculocutaneous albinism, homozygous mutation in the TYR gene), the inher- itance, the clinical picture, the course and the therapeutic and rehabilitative options were explained. Conclusion. Ophthalmogenetic counselling and diagnostics in cases of suspected hereditary eye diseases are crucial for a prompt and a sufficient possible therapy and optical reha- bilitation in affected families. Thorough history analysis and diagnostics can optimise the detection rate and provide rapid and sufficient patient care. Keywords hereditary retinal disease, homozygous mutation, ophthal- mogenetics, juvenile retinischisis, oculocutaneous albinism

Human genetic diagnostics in hereditary eye diseases

Hereditary eye disorders can affect all ocular structures and can be accompanied by structural malformations (e.g. coloboma) or functional disorders (e.g. retinal dystrophy). Ocular phenotypes can also be the presenting symptom of many complex syndromic disorders. The majority of hereditary eye disorders are extremely heterogeneous but can be routinely diagnosed by modern high-throughput sequencing technologies. Molecular testing is highly important not only in in the evaluation of differential diagnoses but is also of increasing relevance due to individual treatment options.

Selective fundus screening for high-risk newborns: a realistic move in the Chinese mainland

Owing to the popularization of fundus screening for high-risk prematurity promoted by the state, the prevention and treatment of retinopathy of prematurity (ROP) in China has achieved remarkable results in recent years. Accordingly, the applicable population scope for newborn fundus screening is under heated discussion. Is it better to screen for all neonates or selective high-risk newborns, who meet the national ROP guidelines, have a history of familial or/and hereditary eye diseases or a systemic disease related to the eye after birth, or show an abnormal eye appearance or suspicious eye diseases in the primary care examination? Despite the advantages of general screening in detecting and treating some malignant eye diseases in a timely manner, the conditions for carrying out general newborn screening are not mature, and there are certain risks in the fundus examination of children. This article points out that the rational use of existing scarce medical resources to carry out selective fundus screening for newborns with high risks of eye diseases is practical in clinical work.

Effect of inbreeding on the occurrence of genetic defects in Chinese Crested dogs

The aim of the study was to analyse the impact of inbreeding on the frequency of hereditary diseases and the number of genetically tested dogs. The pedigrees of 100 Chinese Crested dogs from Polish Kennel Club and information about genetic tests for hereditary eye diseases and other veterinary diagnoses were collected. Inbreeding coefficients and relatedness were estimated for all dogs examined. The relationship between the level of inbreeding and genetic testing was analysed with logistic regression. The relationship between the occurrence of eye disease carriers and sex or the level of inbreeding was also tested. A significant relationship (P &lt; 0.01) was found between inbreeding and the number of animals genetically tested for PLL eye disease. The effect of sex or the level of inbreeding on the eye disease carrier status was non-significant (P &gt; 0.05). However, in some inbred animals the status of the eye disease carrier could be connected with inbreeding, although this needs further research. We found that most of the dogs had related parents and genetic defects. We also found that the breeders often used related dogs, which reduced the genetic diversity of the group and caused hereditary diseases. We suggest that Chinese Crested dog breeders be more open about publishing DNA-test results, which is fundamental for the health of the breed.

Analysis of RPGR gene mutations in 41 Chinese families affected by X-linked inherited retinal dystrophy.

Background: This study analyzed the phenotypes and genotypes of 41 Chinese families with inherited retinal dystrophy (IRD) and RPGR gene mutations. Methods: This retrospective analysis evaluated a cohort of 41 patients who were subjected to a specific Hereditary Eye Disease Enrichment Panel (HEDEP) analysis. All (likely) pathogenic variants were determined by Sanger sequencing, and co-segregation analyses were performed on the available family members. All cases were subjected to Sanger sequencing for RPGR open reading frame 15 (ORF15) mutations. Results: A total of 41 probands from different families with a clinical diagnosis of retinitis pigmentosa (RP; 34 cases) and cone-rod dystrophy (CORD; 7 cases) were included in this cohort. According to clinical information, 2, 18, and 21 cases were first assigned as autosomal dominant (AD), sporadic, and X-linked (XL) inheritance, respectively. Several cases of affected females who presented with a male phenotype have been described, posing challenges at diagnosis related to the apparent family history of AD. Mutations were located in RPGR exons or introns 1–14 and in ORF15 of 12 of 41 (29.3%) and 29 of 41 (70.7%) subjects, respectively. Thirty-four (likely) pathogenic mutations were identified. Frameshifts were the most frequently observed variants, followed by nonsense, splice, and missense mutations. Herein, a detailed description of four RP patients carrying RPGR intronic mutations is reported, and in vitro splice assays were performed to confirm the pathogenicity of these intronic mutations. Conclusion: Our findings provide useful insights for the genetic and clinical counseling of patients with XL IRD, which will be useful for ongoing and future gene therapy trials.

Hereditary Eye Diseases in German Shepherd Dog

Abstract Hereditary eye diseases occur to varying degrees in all dog breeds. Individual purebred breeds have specific predispositions to various eye disorders. The German Shepherd is diagnosed mainly with chronic superficial keratitis/pannus, but also with: distichiasis, plasmoma/atypical pannus, corneal dystrophy, persistent pupillary membranes, cataract, cone degeneration, retinal dysplasia, optic nerve hypoplasia/micropapilla, and limbal melanoma. Individual ocular abnormalities are manifested by characteristic clinical manifestations and ophthalmological findings. Some eye diseases can lead to blindness, others affect the comfort of life or work use of the dog to varying degrees. A thorough knowledge of individual ocular pathologies in a particular breed leads not only to the identification of the diagnosis but also to the correct assessment of the dog’s breeding usability.

Novel variants in PDE6A and PDE6B genes and its phenotypes in patients with retinitis pigmentosa in Chinese families

BackgroundRetinitis pigmentosa (RP) is a genetically heterogeneous disease with 89 causative genes identified to date. However, only approximately 60% of RP cases genetically solved to date, predicating that many novel disease-causing variants are yet to be identified. The purpose of this study is to identify novel variants in PDE6A and PDE6B genes and present its phenotypes in patients with retinitis pigmentosa in Chinese families.MethodsFive retinitis pigmentosa patients with PDE6A variants and three with PDE6B variants were identified through a hereditary eye disease enrichment panel (HEDEP), all patients’ medical and ophthalmic histories were collected, and ophthalmological examinations were performed, followed by an analysis of the possible causative variants. Sanger sequencing was used to verify the variants.ResultsWe identified 20 variants in eight patients: 16 of them were identified in either PDE6A or PDE6B in a compound heterozygous state. Additional four heterozygous variants were identified in the genes ADGRA3, CA4, OPTN, RHO. Two novel genetic changes in PDE6A were identified (c.1246G > A and c.1747 T > A), three novel genetic changes in PDE6B were identified (c.401 T > C, c.2293G > C and c.1610-1612del), out of the novel identified variants one was most probably non-pathogenic (c.2293G > C), all other novel variants are pathogenic. Additional variant was identified in CA4 and RHO, which can cause ADRP (c.243G > A, c.688G > A). In addition, a novel variant in ADGRA3 was identified (c.921-1G > A).ConclusionsThis study reveals novel and known variants in PDE6A and PDE6B genes in Chinese families with autosomal recessive RP, and expands the clinical and genetic findings of photoreceptor-specific enzyme deficiencies.

Эпидемиология наследственных болезней органа зрения в популяциях Российской Федерации

Aim: genetic epidemiological study of hereditary eye diseases in various populations of the Russian Federation and comparative analysis of these findings. Patients and Methods: the sample included 12 ethnic groups from 14 regions of European Russia. The entire population irrespective of gender or age was examined. To confirm a certain type of inheritance of diseases from heterogeneous groups, the material was subjected to the multicomponent analysis used in multiple family registration. The rate of segregation was evaluated using the Weinberg proband method. Molecular genetic tests (Sanger sequencing, MLPA, AFLP, RFLP, whole exome sequencing) were applied. To identify the cases of hereditary disease accumulation in individual populations and/or ethnic groups, the prevalence of certain diseases in this population was calculated using F-distribution to compare the samples of rare diseases. Results: more than 46,000 patients and their relatives with presumably hereditary conditions were examined and data were collected. 554 clinically diverse hereditary diseases in 9,979 individuals were identified. Isolated hereditary eye disease (60 clinical variants) was identifie in 1,407 patients (14.56%). The mean prevalence of isolated hereditary eye disease was 1:2,272 (or 44.01 per 100,000). When assessing patterns of nosological spectrum and prevalence of isolated hereditary eye disease in each population/ethnic group using principal component analysis, 2 clusters were isolated. The first cluster includes 6 Russian populations and the second cluster includes 5 ethnic Volga Region groups, which are more similar to Russian populations than the North Caucasus people. In general, 57 hereditary syndromes (affecting anterior and posterior eye segments) in 1,051 patients were discovered. The mean prevalence of syndromic hereditary eye disease was 1:3,040 (or 32.89 per 100,000). Keywords: ophthalmogenetics, genetic epidemiological study, spectrum, ethnic group, type of inheritance, segregation, accumulation, isolated and syndromic hereditary eye diseases, prevalence, retinal degeneration. For citation: Kadyshev V.V., Ginter E.K., Kutsev S.I. et al. Epidemiology of hereditary eye disease in the populations of Russian Federation. Russian Journal of Clinical Ophthalmology. 2022;22(2):69–79 (in Russ.). DOI: 10.32364/2311-7729-2022-22-2-69-79.

Ocular abnormalities in Polish Hunting Dogs.

This study aimed to describe and determine the prevalence of ocular abnormalities in Polish Hunting Dogs. The study was conducted with 193 Polish Hunting Dogs: 101 female and 92 male animals, aged between 3 months and 12 years. Ophthalmic examinations were performed using slit lamp biomicroscopy, ophthalmoscopy, and tonometry based on the ophthalmological protocol for the examination of hereditary eye diseases. Spectral-domain optical coherence tomography (SD-OCT) was performed for dogs with sudden acquired retinal degeneration syndrome (SARDS) and progressive retinal atrophy (PRA), while electroretinography was also performed in dogs with SARDS. Five dogs (2.6%) were diagnosed with cataract, iris coloboma in 3 dogs (1.6%), ocular dermoid in 1 dog (0.5%), and retinal dysplasia, distichiasis and entropion in 1 dog (1%). Three dogs (1.6%) were diagnosed with PRA and SARDS occurred in 1 dog. Retinal lesions was observed in 16 dogs (8.3%). The clinical signs of retinopathy observed in Polish Hunting Dogs included discoloration of the tapetal fundus, patchy increased reflectivity in the region of discoloration, focus of hyperpigmentation and an area of tapetal hyper-reflectivity with a pigmented center. SD-OCT performed in the 3 dogs with PRA revealed alteration in the retinal layers, which was most advanced in the non-tapetal fundus. Although SD-OCT revealed retinal layers with normal architecture only in some parts of the dorsal, nasal and temporal regions in dogs with SARDS, areas of disorganized external limiting membrane, myeloid zone, ellipsoid zone, outer photoreceptor segment and interdigitation zone were also observed. Polish Hunting Dogs should undergo periodic ophthalmological examination for the evaluation of other hereditary eye diseases. The prevalence of retinal lesions in Polish Hunting Dogs requires further research.

Клініко-епідеміологічні особливості вродженої і спадкової очної патології у дітей

Актуальність. Спадкові та вроджені хвороби очей становлять 60–90 % усіх причин інвалідизуючого зниження зору в дітей. Лікування таких захворювань є малоефективним, а заходи щодо їх профілактики потребують суттєвого вдосконалення. Мета. З’ясування структури та клініко-епідеміологічних особливостей вродженої та спадкової офтальмопатології серед дитячого населення. Матеріали та методи. Були обстежені учні інтернатів для сліпих і слабозорих (максимально зосереджений контингент таких дітей у цих закладах — до 90 %), діти із психоневрологічною патологією (для визначення офтальмологічних проявів при синдромальних ураженнях) міста Києва та діти з вродженою і спадковою очною патологією, які зверталися до Національної дитячої спеціалізованої лікарні «Охматдит» (НДСЛ «Охматдит»). Діагностика генетично детермінованої патології органа зору трактувалась як підозра на спадкову патологію за результатами офтальмологічного обстеження, портретного методу та сімейного анамнезу. Діти з підозрою на очну патологію спадкового характеру скеровувалися для верифікації діагнозу до медико-генетичного центру НДСЛ «Охматдит». Результати. Під час дослідження виявлено, що спадкова та вроджена патологія очей значно обтяжує здоров’я дитячого населення. Спадкові захворювання органа зору учнів інтернатів для сліпих і слабозорих представлені 55 нозологічними формами переважно з аутосомно-домінантним типом успадкування — (40,00 ± 6,61) %. Найчастіше траплялася патологія сітківки і судинного тракту — (30,18 ± 3,53) %, зорового нерва — (24,85 ± 3,32) %, окорухового апарату — (13,61 ± 2,64) %. У (26,04 ± 3,38) % вони мали синдромальний характер. Ці хворби в (79,29 ± 3,12) % маніфестували при народженні, що визначає можливі терміни їх ранньої діагностики та початку реабілітації. Серед дітей із психоневрологічною патологією виявлено перевагу аномалій рефракції та патологію окорухового апарату, що були проявами синдромальних уражень. Висновки. Доведено, що існує можливість підозри генетично детермінованого характеру патології очей на основі результатів амбулаторного обстеження та збору сімейного анамнезу офтальмологом на амбулаторному прийомі.