Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
5.6
Journals
IJMS
Special Issues
Genetics of Eye Disease 2.0
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Genetics of Eye Disease 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 10505

Special Issue Editor

Prof. Dr. Tomasz Żarnowski

E-Mail Website
Guest Editor
Department of Diagnostics and Microsurgery of Glaucoma, Medical University of Lublin, 20-059 Lublin, Poland
Interests: management of glaucoma (wound healing, complications, new methods); neuroprotection in neuroscience (glaucoma, epilepsy); glaucoma genetics; clinico-genetical correlations; management of complicated cataracts
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Genetics of eye diseases has been a field of interest for many researchers in the last few decades. Technological advancement of molecular techniques allowed the spread of new approaches in search of genetic factors underlying pathological processes in ocular disorders. For years, traditional linkage analysis has been utilized to link different diseases' phenotypes with particular loci and has been successful in finding variations responsible for known pathological processes, for instance in retinoblastoma. One limitation of this approach is its reliance on prior knowledge of pathological pathways. Most eye diseases are clinically heterogenous, with many pathways still unknown. Additionally, diseases’ phenotypical heterogeneity is usually reflected by their polygenic inheritance, therefore linkage analysis, though useful in finding genes of big impact, fails to recognize whole spectrum of casual variations involved in development of complex diseases, such as glaucoma, age-related maculopathy or keratoconjunctivitis sicca. In age-related maculopathy, which is considered the most well genetically defined complex disorder, two major loci explain only half of its heritability and MYOC, one of major glaucoma-causing genes is present only in 2–4% of primary open-angle glaucoma patients. More recently, genome-wide association studies have emerged. These huge studies are more powerful in finding variations in genes of subtle effects that summarily contribute to more complex disorders, thus they are hoped, among others, to help defining heritability of polygenic eye diseases. Importance of knowledge regarding genetics of eye diseases is hard to overestimate, especially up against novel achievements of molecular manipulation techniques. Advances in sequence analysis and gene delivery methods, by both viral and nonviral vectors have recently allowed the delivery of genetic payloads in preclinical models of retinal disorders, expanding the disease-modifying power of gene therapies. Further studies regarding targets for such therapies are however still needed. Despite the number of studies contributing to different eye diseases’ genetics there is still little understood and much to be revealed.

This special issue is focused on molecular side of the topic, nevertheless clinical implications are also welcome, if connected with biomolecular experiments.

Prof. Dr. Tomasz Żarnowski
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gene phenotypes
  • genetic payloads
  • retinoblastoma
  • glaucoma
  • age-related maculopathy
  • keratoconjunctivitis sicca
  • gene delivery methods

Related Special Issue

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 5252 KiB  
Article
Genetic and Clinical Profile of Retinopathies Due to Disease-Causing Variants in Leber Congenital Amaurosis (LCA)-Associated Genes in a Large German Cohort
by Ditta Zobor, Britta Brühwiler, Eberhart Zrenner, Nicole Weisschuh and Susanne Kohl
Int. J. Mol. Sci. 2023, 24(10), 8915; https://doi.org/10.3390/ijms24108915 - 17 May 2023
Cited by 5 | Viewed by 1679
Abstract
To report the spectrum of Leber congenital amaurosis (LCA) associated genes in a large German cohort and to delineate their associated phenotype. Local databases were screened for patients with a clinical diagnosis of LCA and for patients with disease-causing variants in known LCA-associated [...] Read more.
To report the spectrum of Leber congenital amaurosis (LCA) associated genes in a large German cohort and to delineate their associated phenotype. Local databases were screened for patients with a clinical diagnosis of LCA and for patients with disease-causing variants in known LCA-associated genes independent of their clinical diagnosis. Patients with a mere clinical diagnosis were invited for genetic testing. Genomic DNA was either analyzed in a diagnostic-genetic or research setup using various capture panels for syndromic and non-syndromic IRD (inherited retinal dystrophy) genes. Clinical data was obtained mainly retrospectively. Patients with genetic and phenotypic information were eventually included. Descriptive statistical data analysis was performed. A total of 105 patients (53 female, 52 male, age 3–76 years at the time of data collection) with disease-causing variants in 16 LCA-associated genes were included. The genetic spectrum displayed variants in the following genes: CEP290 (21%), CRB1 (21%), RPE65 (14%), RDH12 (13%), AIPL1 (6%), TULP1 (6%), and IQCB1 (5%), and few cases harbored pathogenic variants in LRAT, CABP4, NMNAT1, RPGRIP1, SPATA7, CRX, IFT140, LCA5, and RD3 (altogether accounting for 14%). The most common clinical diagnosis was LCA (53%, 56/105) followed by retinitis pigmentosa (RP, 40%, 42/105), but also other IRDs were seen (cone-rod dystrophy, 5%; congenital stationary night blindness, 2%). Among LCA patients, 50% were caused by variants in CEP290 (29%) and RPE65 (21%), whereas variants in other genes were much less frequent (CRB1 11%, AIPL1 11%, IQCB1 9%, and RDH12 7%, and sporadically LRAT, NMNAT1, CRX, RD3, and RPGRIP1). In general, the patients showed a severe phenotype hallmarked by severely reduced visual acuity, concentric narrowing of the visual field, and extinguished electroretinograms. However, there were also exceptional cases with best corrected visual acuity as high as 0.8 (Snellen), well-preserved visual fields, and preserved photoreceptors in spectral domain optical coherence tomography. Phenotypic variability was seen between and within genetic subgroups. The study we are presenting pertains to a considerable LCA group, furnishing valuable comprehension of the genetic and phenotypic spectrum. This knowledge holds significance for impending gene therapeutic trials. In this German cohort, CEP290 and CRB1 are the most frequently mutated genes. However, LCA is genetically highly heterogeneous and exhibits clinical variability, showing overlap with other IRDs. For any therapeutic gene intervention, the disease-causing genotype is the primary criterion for treatment access, but the clinical diagnosis, state of the retina, number of to be treated target cells, and the time point of treatment will be crucial. Full article
(This article belongs to the Special Issue Genetics of Eye Disease 2.0)
►▼ Show Figures

Figure 1

16 pages, 3050 KiB  
Article
Variant Landscape of 15 Genes Involved in Corneal Dystrophies: Report of 30 Families and Comprehensive Analysis of the Literature
by Di Zhu, Junwen Wang, Yingwei Wang, Yi Jiang, Shiqiang Li, Xueshan Xiao, Panfeng Wang and Qingjiong Zhang
Int. J. Mol. Sci. 2023, 24(5), 5012; https://doi.org/10.3390/ijms24055012 - 6 Mar 2023
Cited by 1 | Viewed by 2586
Abstract
Corneal dystrophies (CDs) represent a group of inherited diseases characterized by the progressive deposit of abnormal materials in the cornea. This study aimed to describe the variant landscape of 15 genes responsible for CDs based on a cohort of Chinese families and a [...] Read more.
Corneal dystrophies (CDs) represent a group of inherited diseases characterized by the progressive deposit of abnormal materials in the cornea. This study aimed to describe the variant landscape of 15 genes responsible for CDs based on a cohort of Chinese families and a comparative analysis of literature reports. Families with CDs were recruited from our eye clinic. Their genomic DNA was analyzed using exome sequencing. The detected variants were filtered using multi-step bioinformatics and confirmed using Sanger sequencing. Previously reported variants in the literature were summarized and evaluated based on the gnomAD database and in-house exome data. In 30 of 37 families with CDs, 17 pathogenic or likely pathogenic variants were detected in 4 of the 15 genes, including TGFBI, CHST6, SLC4A11, and ZEB1. A comparative analysis of large datasets revealed that 12 of the 586 reported variants are unlikely causative of CDs in monogenic mode, accounting for 61 of 2933 families in the literature. Of the 15 genes, the gene most frequently implicated in CDs was TGFBI (1823/2902, 62.82% of families), followed by CHST6 (483/2902, 16.64%) and SLC4A11 (201/2902, 6.93%). This study presents, for the first time, the landscape of pathogenic and likely pathogenic variants in the 15 genes responsible for CDs. Awareness of frequently misinterpreted variants, such as c.1501C>A, p.(Pro501Thr) in TGFBI, is crucial in the era of genomic medicine. Full article
(This article belongs to the Special Issue Genetics of Eye Disease 2.0)
►▼ Show Figures

Figure 1

12 pages, 996 KiB  
Article
Casitas B-lineage lymphoma Gene Mutation Ocular Phenotype
by Christine Fardeau, Munirah Alafaleq, Marie-Adélaïde Ferchaud, Miguel Hié, Caroline Besnard, Sonia Meynier, Frédéric Rieux-Laucat, Damien Roos-Weil, Fleur Cohen and Isabelle Meunier
Int. J. Mol. Sci. 2022, 23(14), 7868; https://doi.org/10.3390/ijms23147868 - 17 Jul 2022
Cited by 2 | Viewed by 1692
Abstract
This article describes the ocular phenotype associated with the identified Casitas B-lineage lymphoma (CBL) gene mutation and reviews the current literature. This work also includes the longitudinal follow-up of five unrelated cases of unexplained fundus lesions with visual loss associated with [...] Read more.
This article describes the ocular phenotype associated with the identified Casitas B-lineage lymphoma (CBL) gene mutation and reviews the current literature. This work also includes the longitudinal follow-up of five unrelated cases of unexplained fundus lesions with visual loss associated with a history of hepatosplenomegaly. Wide repeated workup was made to rule out infections, inflammatory diseases, and lysosomal diseases. No variants in genes associated with retinitis pigmentosa, cone–rod dystrophy, and inherited optic neuropathy were found. Molecular analysis was made using next-generation sequencing (NGS) and whole-exome sequencing (WES). The results included two cases sharing ophthalmological signs including chronic macular edema, vascular leakage, visual field narrowing, and electroretinography alteration. Two other cases showed damage to the optic nerve head and a fifth young patient exhibited bilateral complicated vitreoretinal traction and carried a heterozygous mutation in the CBL gene associated with a mutation in the IKAROS gene. Ruxolitinib as a treatment for RASopathy did not improve eye conditions, whereas systemic lesions were resolved in one patient. Mutations in the CBL gene were found in all five cases. In conclusion, a detailed description may pave the way for the CBL mutation ocular phenotype. Genetic analysis using whole-exome sequencing could be useful in the diagnosis of unusual clinical features. Full article
(This article belongs to the Special Issue Genetics of Eye Disease 2.0)
►▼ Show Figures

Figure 1

24 pages, 8835 KiB  
Article
The Clinical Spectrum and Disease Course of DRAM2 Retinopathy
by Tjaša Krašovec, Marija Volk, Maja Šuštar Habjan, Marko Hawlina, Nataša Vidović Valentinčič and Ana Fakin
Int. J. Mol. Sci. 2022, 23(13), 7398; https://doi.org/10.3390/ijms23137398 - 2 Jul 2022
Cited by 3 | Viewed by 2020
Abstract
Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene (DRAM2) cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two Slovenian patients harboring a novel DRAM2 variant and a detailed review of all [...] Read more.
Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene (DRAM2) cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two Slovenian patients harboring a novel DRAM2 variant and a detailed review of all 23 other patients described to date. Whole exome and whole genome sequencing were performed in the two patients, and both underwent ophthalmological examination with a 2-year follow-up. PubMed was searched for papers with clinical descriptions of DRAM2 retinopathy. Patient 1 was homozygous for a novel variant, p.Met1?, and presented with the acute onset of photopsia and retina-wide retinopathy at the age of 35 years. The patient was first thought to have an autoimmune retinopathy and was treated with mycophenolate mofetil, which provided some symptomatic relief. Patient 2 was compound heterozygous for p.Met1? and p.Leu246Pro and presented with late-onset maculopathy at the age of 59 years. On review, patients with DRAM2 retinopathy usually present in the third decade with central visual loss, outer retinal layer loss on optical coherence tomography and a hyperautofluorescent ring on fundus autofluorescence. Either cone–rod or rod–cone dystrophy phenotype is observed on electroretinography, reflecting the importance of DRAM2 in both photoreceptor types. Non-null variants can result in milder disease. Full article
(This article belongs to the Special Issue Genetics of Eye Disease 2.0)
►▼ Show Figures

Figure 1

Review

Jump to: Research

11 pages, 265 KiB  
Review
Relative Frequencies of PAX6 Mutational Events in a Russian Cohort of Aniridia Patients in Comparison with the World’s Population and the Human Genome
by Tatyana A. Vasilyeva, Andrey V. Marakhonov, Sergey I. Kutsev and Rena A. Zinchenko
Int. J. Mol. Sci. 2022, 23(12), 6690; https://doi.org/10.3390/ijms23126690 - 15 Jun 2022
Cited by 2 | Viewed by 1734
Abstract
Genome-wide sequencing metadata allows researchers to infer bias in the relative frequencies of mutational events and to predict putative mutagenic models. In addition, much less data could be useful in the evaluation of the mutational frequency spectrum and the prevalent local mutagenic process. [...] Read more.
Genome-wide sequencing metadata allows researchers to infer bias in the relative frequencies of mutational events and to predict putative mutagenic models. In addition, much less data could be useful in the evaluation of the mutational frequency spectrum and the prevalent local mutagenic process. Here we analyzed the PAX6 gene locus for mutational spectra obtained in our own and previous studies and compared them with data on other genes as well as the whole human genome. MLPA and Sanger sequencing were used for mutation searching in a cohort of 199 index patients from Russia with aniridia and aniridia-related phenotypes. The relative frequencies of different categories of PAX6 mutations were consistent with those previously reported by other researchers. The ratio between substitutions, small indels, and chromosome deletions in the 11p13 locus was within the interval previously published for 20 disease associated genomic loci, but corresponded to a higher end due to very high frequencies of small indels and chromosome deletions. The ratio between substitutions, small indels, and chromosome deletions for disease associated genes, including the PAX6 gene as well as the share of PAX6 missense mutations, differed considerably from those typical for the whole genome. Full article
(This article belongs to the Special Issue Genetics of Eye Disease 2.0)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop