CLINICAL/DEMOGRAPHIC, FUNCTIONAL TESTING AND MULTIMODAL IMAGING DIFFERENCES BETWEEN GENETICALLY SOLVED AND UNSOLVED RETINITIS PIGMENTOSA

2021 ◽  
Author(s):  
João Pedro Marques ◽  
Ana Marta ◽  
Sara Geada ◽  
Ana Luísa Carvalho ◽  
Pedro Menéres ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Retinitis Pigmentosa ◽  
Multimodal Imaging ◽  
Cross Sectional Study ◽  
Retinal Layer ◽  
Functional Testing ◽  
Imaging Features ◽  
Cross Sectional ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies

INTRODUCTION The purpose of this study was to compare clinical/demographic, functional testing and multimodal imaging features between genetically solved and genetically unsolved non-syndromic retinitis pigmentosa (nsRP) patients. METHODS Cross sectional study conducted at an inherited retinal dystrophies reference center. Consecutive patients with nsRP and available genetic testing results performed between 2018 and 2020 were included. Genetic testing was clinically-oriented and variants were classified according to the American College of Medical Genetics and Genomics. Only class IV or V variants were considered disease-causing. Clinical/demographic, functional and imaging features were compared between genetically unsolved (G1) and genetically solved (G2) patients. RESULTS A total of 175 patients (146 families) were included: 68 patients (59 families) in G1 and 107 patients (87 families) in G2. First symptoms <25 years, consanguinity, evidence for a particular inheritance pattern and absence of indicators for phenocopies were significantly more prevalent in G2. No significant differences were observed on best-corrected visual acuity. The visual field index and mean central retinal layer thickness were significantly higher in G1. The frequency of atypical features on multimodal imaging did not differ between groups. CONCLUSION Individual clinical/demographic, functional testing and multimodal imaging features should be considered when counselling patients about the probability of identifying disease-causing variants.

scholarly journals Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Irene Perea-Romero ◽  
◽  
Gema Gordo ◽  
Ionut F. Iancu ◽  
Marta Del Pozo-Valero ◽  
...  
Keyword(s):  
Genetic Diagnosis ◽  
Cross Sectional Study ◽  
Molecular Techniques ◽  
Cross Sectional ◽  
Autonomous Communities ◽  
Inherited Retinal Dystrophies ◽  
Pathogenic Variants ◽  
Retinal Dystrophies ◽  
Family Pedigree ◽  
Genetic Landscape

AbstractInherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.

Patient Use of Dietary Supplements, Home Monitoring, or Genetic Testing for Nonneovascular Age-Related Macular Degeneration

2021 ◽  
pp. 247412642198922
Author(s):  
Brittany C. Tsou ◽  
T.Y. Alvin Liu ◽  
Jun Kong ◽  
Susan B. Bressler ◽  
J. Fernando Arevalo ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Macular Degeneration ◽  
Dietary Supplements ◽  
Home Monitoring ◽  
Cross Sectional Study ◽  
Age Related Macular Degeneration ◽  
Cross Sectional ◽  
Supplement Use ◽  
Age Related ◽  
Disease Study

Purpose: This work evaluated the use and type of dietary supplements and home monitoring for nonneovascular age-related macular degeneration (AMD), as well as the prevalence of genetic testing among patients with AMD. Methods: A cross-sectional study was conducted of 129 participants older than 50 years who completed self-administered questionnaires regarding usage and type of dietary supplements and home monitoring, as well as the participants’ use of genetic testing for AMD. Results: Of 91 participants with AMD, 83 (91.2%) took vitamins, including 55 (60.4%) who used an Age-Related Eye Disease Study (AREDS) or AREDS2 formulation. Of 38 without AMD, 31 (81.6%) took vitamins (difference from participants with AMD = 9.6% [95% CI, 0%-23.2%]), including 2 on an AREDS formulation. Among 82 participants with AMD who were AREDS candidates (intermediate or advanced AMD in 1 or both eyes), 51 (62.2%; 95% CI, 51.7%-72.7%) took an AREDS or AREDS2 formulation, and 31 (37.8%) did not (5 were unsure). Additionally, 50 (61.0%; 95% CI, 50.4%-71.6%) AREDS candidates did some type of home monitoring. Only 1 (1.2%; 95% CI, 0%-3.6%) underwent genetic testing for AMD. Among 9 with AMD who were not AREDS candidates, 4 (44.4%) used an AREDS formulation, 4 (44.4%) did not, and 1 (11.1%) was unsure; only 1 (11.1%) of these 9 performed home monitoring. Conclusions: Despite similar results from past surveys and AREDS2 data supporting supplement use in 2013 and home monitoring in 2014, these findings suggest about one-third of AREDS candidates do not do so, providing further support for improving education regarding appropriate supplement and home monitoring usage. Genetic testing for AMD also appears infrequent.

scholarly journals Knowledge and attitude toward genetic diseases and genetic tests among pre-marriage individuals: A cross-sectional study in northern Iran

2019 ◽  
Author(s):  
Mohammad Bagher Hashemi-Soteh ◽  
Ali Vali Nejad ◽  
Golamreza Ataei ◽  
Dariush Ghasemi ◽  
Rita Siamy
Keyword(s):  
Genetic Counseling ◽  
Genetic Testing ◽  
Genetic Diseases ◽  
Cross Sectional Study ◽  
Or Education ◽  
Genetic Tests ◽  
Northern Iran ◽  
Cross Sectional ◽  
Hereditary Disorders ◽  
Knowledge And Attitude

Background: Genetic testing has been widely introduced for many hereditary disorders. While the attitudes towards these facilities have been evaluated in many countries, there are only a few reports on the knowledge of and the orientation among Iranians. Objective: The current study assesses the attitudes and knowledge of pre-marriage individuals toward the availability and use of genetic tests. Materials and Methods: A comprehensive questionnaire was distributed among 408 marrying individuals. The questions addressed the demographic characteristics along the registration of participant’s knowledge, education, and attitude toward genetic testing. The individuals were divided into three groups based on their knowledge: 1) Scored above 80 to 100 were defined as “good” 2) 60 to 80 as “average” 3) less than 60 as “poor” knowledge. Result: Most participants (86%) believed consanguineous marriages increase the risk of genetic diseases; 82.3% knew that thalassemia is a type of genetic disease, only 33.3% could distinguish prenatal diagnosis (PND) from other laboratory tests. The relationship between the participants’ knowledge and their level of education was significant (r = 0.78, p < 0.001), age (r =–0.16, p < 0.01), and urbanity (p < 0.01). A prominent relationship was observed between the knowledge (r = 0.64, p < 0.001) or education (r = 0.62, p < 0.001) and people’s desire to use the genetic tests before the wedding ceremony. No significant correlations were found between the participant’s attitude and their ages/urbanity. Most of the individuals agreed to arrange a genetic counseling before marriage (0.94%). Conclusion: This study revealed that most individuals were interested in using genetic counseling services and genetic tests before marriage.

scholarly journals Genome Editing as a Treatment for the Most Prevalent Causative Genes of Autosomal Dominant Retinitis Pigmentosa

2019 ◽  
Vol 20 (10) ◽  
pp. 2542 ◽  
Author(s):  
Michalitsa Diakatou ◽  
Gaël Manes ◽  
Beatrice Bocquet ◽  
Isabelle Meunier ◽  
Vasiliki Kalatzis
Keyword(s):  
Retinitis Pigmentosa ◽  
Genome Editing ◽  
Mutant Allele ◽  
Autosomal Dominant ◽  
Dominant Negative ◽  
Therapeutic Approaches ◽  
Autosomal Dominant Retinitis Pigmentosa ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Type Gene

Inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of diseases with more than 250 causative genes. The most common form is retinitis pigmentosa. IRDs lead to vision impairment for which there is no universal cure. Encouragingly, a first gene supplementation therapy has been approved for an autosomal recessive IRD. However, for autosomal dominant IRDs, gene supplementation therapy is not always pertinent because haploinsufficiency is not the only cause. Disease-causing mechanisms are often gain-of-function or dominant-negative, which usually require alternative therapeutic approaches. In such cases, genome-editing technology has raised hopes for treatment. Genome editing could be used to (i) invalidate both alleles, followed by supplementation of the wild type gene, (ii) specifically invalidate the mutant allele, with or without gene supplementation, or (iii) to correct the mutant allele. We review here the most prevalent genes causing autosomal dominant retinitis pigmentosa and the most appropriate genome-editing strategy that could be used to target their different causative mutations.

scholarly journals Cross-sectional study of smoking exposure: no differential effect on OCT metrics in a cohort of MS patients

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731982840 ◽  
Author(s):  
Mattia Rosso ◽  
Dorlan J Kimbrough ◽  
Cindy T Gonzalez ◽  
Bonnie I Glanz ◽  
Brian C Healy ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Cross Sectional Study ◽  
Smoking History ◽  
Retinal Layer ◽  
Fiber Layer ◽  
Cross Sectional ◽  
Macular Volume ◽  
Smoking Exposure ◽  
Significant Difference ◽  
Never Smokers

Background Optical coherence tomography (OCT) provides quantitative measures of retinal layer thickness. Cigarette smoking is a risk factor for multiple sclerosis (MS) onset and disease severity: its effects on OCT metrics have not been assessed. Objective The objective of this study was to assess the effect of smoking history on retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform (GCIP) of MS patients by OCT. Methods 112 MS patients were recruited from the Brigham and Women’s Hospital. Spectralis OCT scans were acquired to measure GCIP, peripapillary RNFL, and total macular volume. Multivariable linear mixed effects regression model assessed RNFL and GCIP change with fixed effects for smoking history while adjusting for optic neuritis eye status, age, disease duration, sex, baseline EDSS, and disease modifying therapies (DMTs). Results Smoking histories were available for 102 patients: 46 (45.10%) had a history of smoking cigarettes and 56 (54.90%) never smoked. No statistically significant differences were found between ever-smokers and never-smokers with respect to GCIP, RNFL, and macular volume. Conclusion Our study shows no significant difference in retinal thickness between ever-smokers and never-smokers. If confirmed, this result suggests mechanistic differences between the retina and other central nervous system (CNS) compartments in response to smoking and should be noted when considering OCT as a surrogate measure of CNS activity.

scholarly journals Parent Knowledge of Screening and Genetic Testing in Retinoblastoma

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Wei Xiao ◽  
Xian Ji ◽  
Huijing Ye ◽  
Huiqi Zeng ◽  
Yang Gao ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Southern China ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Parent Knowledge ◽  
Face To Face ◽  
Related Information ◽  
Health Related ◽  
Oncology Unit

Purpose. To evaluate parent knowledge of screening and genetic testing for retinoblastoma and its potential correlation with demographics, clinical features, and socioeconomical factors. Methods. It was a cross-sectional study conducted at the ocular oncology unit of a tertiary ophthalmic center in Southern China. A face-to-face interview was administered to parents of retinoblastoma children during hospitalization. Parent knowledge was assessed using the sum score of a 7-item questionnaire. Demographics and socioeconomic status were collected from the interview, and clinical data were retrieved from the medical records. Results. A total of 126 parents of retinoblastoma children were included. Parents accurately answered 66.7% to 84.9% of each item in the questionnaire. Only 37 (29.4%) parents correctly answered all 7 questions. Parent knowledge was positively correlated with education, but it was not associated with patients’ laterality, sex, or household income. Physicians and the Internet were the major sources of parental health-related information. During the median follow-up of 492 days, 13 (61.9%) of 21 patients in the full-score group without genetic testing at baseline actually conducted testing during follow-up compared to 29 of 67 (43.3%) in the less-than-full-score group (P=0.136). Conclusion. Overall parent knowledge about retinoblastoma screening and genetic testing was moderate. Higher education was associated with greater parent knowledge. Future studies should validate our findings in other populations, especially in those with different cultural background and healthcare systems.

scholarly journals Diagnostic practices and disease surveillance in Canadian children with congenital central hypoventilation syndrome

2013 ◽  
Vol 20 (3) ◽  
pp. 165-170 ◽  
Author(s):  
Reshma Amin ◽  
Theo J Moraes ◽  
Amy Skitch ◽  
Meredith S Irwin ◽  
Stephen Meyn ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Disease Surveillance ◽  
Cross Sectional Study ◽  
Policy Statement ◽  
Congenital Central Hypoventilation Syndrome ◽  
Cross Sectional ◽  
Web Based ◽  
Diagnostic Practices ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

OBJECTIVE: To assess the diagnostic and surveillance practices of Canadian pediatric subspecialists for children with congenital central hypoventilation syndrome (CCHS).METHODS: The present analysis was a prospective cross-sectional study. A web-based survey was sent to 303 pediatric subspecialists in Canada: 85 pediatric respirologists, 77 pediatric neurologists and 141 neonatologists. The survey included 36 questions about the current diagnostic and surveillance management of pediatric CCHS. Differences in responses among respirologists, neurologists and neonatologists were evaluated for each question, where feasible, and responses were compared with the 2010 American Thoracic Society (ATS) Clinical Policy Statement for CCHS.RESULTS: A total of 83 (27%) participants responded to the survey; the highest survey response rate (40%) was from respirologists. For the diagnosis of CCHS, 25% of respondents did not order genetic testing, either alone or with another test, to make a diagnosis of CCHS. The criteria and tests recommended by the ATS to make a diagnosis of CCHS – genetic testing, diagnosis of exclusion, polysomnogram and plus or minus a hypercapnic challenge – were ordered by 23 (43%) of the 54 respondents. Although polysomnograms were ordered for more than 90% of children with CCHS, only 37% of respirologists aimed for a carbon dioxide range of 35 mmHg to 40 mmHg during polysomnogram titrations.CONCLUSIONS: The results demonstrate variability in the diagnostic and surveillance practices of pediatric subspecialists in children with CCHS across Canada. The present study provides an initial needs assessment and demonstrated that there are significant deviations in practice from the 2010 ATS guidelines.

scholarly journals Evaluation of retinal sensitivity and microstructure in areas of capillary nonperfusion of eyes with branch retinal vein occlusion

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Puying Wei ◽  
Chenchen Liu ◽  
Yanzhen Zhang ◽  
Liu Yang
Keyword(s):  
Optical Coherence Tomography ◽  
Cross Sectional Study ◽  
Retinal Sensitivity ◽  
Imaging Features ◽  
Optical Coherence ◽  
Cross Sectional ◽  
Multiple Modalities ◽  
Microstructure Changes ◽  
Retinal Layers ◽  
Vein Occlusion

Abstract Background To evaluate macular microstructure alterations in the parafoveal nonperfusion areas of eyes with branch retinal vein occlusions (BRVO), and to investigate their impact on retinal sensitivity. Methods This was a cross-sectional study including thirteen BRVO patients with parafoveal capillary nonperfusion areas (NPA). Multiple modalities including microperimetry, optical coherence tomography angiography, and optical coherence tomography were performed to measure retinal sensitivity and thickness, and to identify the microstructure changes and perfusion status. Results The retinal sensitivity and thickness in the NPA were significantly lower than those in the perfusion areas (PA) (P = 0.001, P = 0.003). Microstructure changes, including disorganization of the retinal inner layers (DRIL), disruption of the outer retinal layers, and cysts were more frequently observed in NPA (P = 0.002, P = 0.018, P = 0.068). Within NPA, the retinal sensitivity of areas with DRIL, and outer retinal layers disruption was significantly lower than that of the areas without DRIL (P = 0.016), and with intact outer retinal layers (P < 0.001), respectively. 1dB increase in retinal sensitivity was correlated with 2.2 μm (95 % confidence interval, 1.71–2.7) increase of the thickness (P < 0.001). The retinal sensitivity was significantly lower at points with both DRIL and outer retinal layers disruption than at the points with DRIL or outer retina layers disruption alone (P = 0.001, P = 0.001). Conclusions Alterations in the macular microstructure are associated with ischemia, especially DRIL. DRIL and outer retinal layers disruption are imaging features that have important implications for local retinal sensitivity in the ischemic areas, and where the microstructure of both inner and outer retinal layers is disrupted the function is further destructed.

scholarly journals Investigating the knowledge of and public attitudes towards genetic testing within the Visegrad countries: a cross-sectional study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Klára Bíró ◽  
Viktor Dombrádi ◽  
Zita Fekete ◽  
Gábor Bányai ◽  
Klára Boruzs ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Sex Education ◽  
Robust Regression ◽  
Nuclear Family ◽  
Public Attitudes ◽  
Cross Sectional Study ◽  
Genetic Determinism ◽  
Sectional Study ◽  
Cross Sectional ◽  
Visegrád Countries

Abstract Background Previous studies have investigated various factors that can determine the attitudes of the citizens considering genetic testing. However, none of them investigated how these attitudes may differ between the Visegrad countries. Methods In this cross-sectional study a questionnaire developed by Dutch researchers was translated and used in Hungary, Slovakia, Czechia and Poland. In each country 1000 adult citizens were asked on the topics of personal benefits regarding genetic tests, genetic determinism, and finally, the availability and usage of genetic testing. Multivariate robust regression model was created including several possible influencing factors (such as age, sex, education, marital status, religiousness, and having a genetic test within the nuclear family) to identify the possible differences between the four countries. Results The Hungarian citizens had the most positive opinion on the personal benefits of genetic testing followed by the Czech, Slovak and Polish. All differences were significant in this regard. Considering genetic determinism, the Slovak citizens had a significantly firmer belief in this issue compared to the Hungarians. No other significant differences were observed in this domain. On the topic of the availability and use of genetic testing the Hungarian citizens had the most accepting opinion among the four countries, followed by the Czech citizens. In this domain the Polish and Slovak answers did not differ significantly from each other. Conclusions Significant differences were observed even when considering various confounding effects. As the underlying reasons for these discrepancies are unknown, future studies should investigate this enigma among the four countries.

scholarly journals Comprehensive Geno- and Phenotyping in a Complex Pedigree Including Four Different Inherited Retinal Dystrophies

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 137
Author(s):  
Johannes Birtel ◽  
Martin Gliem ◽  
Kristina Hess ◽  
Theresa H. Birtel ◽  
Frank G. Holz ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Night Blindness ◽  
Molecular Genetic ◽  
Cone Dystrophy ◽  
Molecular Testing ◽  
Congenital Stationary Night Blindness ◽  
Molecular Genetic Testing ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Novel Variant

Inherited retinal dystrophies (IRDs) are characterized by high clinical and genetic heterogeneity. A precise characterization is desirable for diagnosis and has impact on prognosis, patient counseling, and potential therapeutic options. Here, we demonstrate the effectiveness of the combination of in-depth retinal phenotyping and molecular genetic testing in complex pedigrees with different IRDs. Four affected Caucasians and two unaffected relatives were characterized including multimodal retinal imaging, functional testing, and targeted next-generation sequencing. A considerable intrafamilial phenotypic and genotypic heterogeneity was identified. While the parents of the index family presented with rod-cone dystrophy and ABCA4-related retinopathy, their two sons revealed characteristics in the spectrum of incomplete congenital stationary night blindness and ocular albinism, respectively. Molecular testing revealed previously described variants in RHO, ABCA4, and MITF as well as a novel variant in CACNA1F. Identified variants were verified by intrafamilial co-segregation, bioinformatic annotations, and in silico analysis. The coexistence of four independent IRDs caused by distinct mutations and inheritance modes in one pedigree is demonstrated. These findings highlight the complexity of IRDs and underscore the need for the combination of extensive molecular genetic testing and clinical characterization. In addition, a novel variant in the CACNA1F gene is reported associated with incomplete congenital stationary night blindness.

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