Special Issue "Inherited Retinal Disease: Novel Candidate Genes, Genotype–Phenotype Correlations and Inheritance Models"

A special issue of Genes (ISSN 2073-4425).

Deadline for manuscript submissions: 31 August 2017

Special Issue Editors

Guest Editor
Prof. Dr. Frans P.M. Cremers

Department of Human Genetics and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
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Interests: genetics of inherited retinal dystrophies; Stargardt disease; genomics; stem cell technology; transcriptomics; non-coding variants
Co-Guest Editor
Prof. Dr. Camiel J.F. Boon

Department of Ophthalmology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; Department of Ophthalmology, Academic Medical Center, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands
Website | E-Mail
Interests: clinical and genetic characteristics of inherited retinal diseases; gene therapy; central serous chorioretinopathy; age-related macular degeneration; vitreoretinal surgery
Co-Guest Editor
Dr. Kinga Bujakowska

Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, MA 02114, USA
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Interests: genetics of inherited retinal degenerations, modeling of the inherited retinal degenerations in cell, zebrafish and mouse models
Co-Guest Editor
Dr. Christina Zeitz

INSERM, UMR_S968, CNRS, UMR_7210, Université Pierre et Marie Curie Paris 6 Institut de la Vision, Department of Genetics, 17, rue Moreau, 75012 Paris, France
Website | E-Mail
Interests: Gene defect identification underlying progressive and non progressive retinal disorders, prevalence studies, prepare patients for therapeutic trials, in vitro and in vivo functional analysis of novel gene defects, gene therapies, decipher retinal signaling

Special Issue Information

Dear Colleagues,

Knowledge on the genetic defects and molecular mechanisms underlying inherited retinal diseases (IRDs) has steadily grown in the last three decades. Based on comprehensive genotyping studies (e.g., using whole-exome sequencing, WES) we can deduce that the majority of genetic defects can be found in the currently identified ~150 genes implicated in non-syndromic IRDs. The downside of this huge genetic heterogeneity is that we are now facing new challenges to identify the remaining genetic causes. An increasing number of candidate IRD genes is being identified which are mutated in a single patient or family. Due to the large genetic heterogeneity in IRDs, a significant proportion of healthy individuals and IRD cases carry heterozygous variants in one or a few IRD-associated genes. This could be coincidental findings, but also may mean that we are missing ‘second alleles’ because of their location outside the coding segments that are not analyzed using WES. We are beginning to understand the complex interplay between variants in different IRD genes and still need to investigate the nature of modifiers in IRD-associated genes and in other genes, and how they influence the clinical characteristics in patients. Importantly, knowing the genetic defects and molecular mechanisms of disease is not only important for accurate genetic counseling and disease prognosis, but also is necessary to select patients for gradually emerging therapies, many of which are based on knowledge of the mutated gene or genetic variant(s).This issue is not meant to include papers on multifactorial eye diseases, such as age-related macular degeneration, glaucoma or myopia, unless they deal with familial forms of these macular degeneration or glaucoma. We also do not invite paper submissions on therapeutics of IRDs.

Prof. Dr. Frans P.M. Cremers
Guest Editor

Prof. Dr. Camiel J.F. Boon
Dr. Kinga Bujakowska
Dr. Christina Zeitz
Co-Guest Editors

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 papers will be 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. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1200 CHF (Swiss Francs). 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

  • Retina
  • Genetics
  • Ophthalmology
  • Retinitis pigmentosa
  • Modifiers
  • Genomics
  • Digenic inheritance

Published Papers (3 papers)

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Research

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Open AccessArticle EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression
Genes 2017, 8(7), 178; doi:10.3390/genes8070178
Received: 6 May 2017 / Revised: 6 July 2017 / Accepted: 6 July 2017 / Published: 12 July 2017
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Abstract
Mutations in the EYS (eyes shut homolog) gene are a common cause of autosomal recessive (ar) retinitis pigmentosa (RP). Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal
[...] Read more.
Mutations in the EYS (eyes shut homolog) gene are a common cause of autosomal recessive (ar) retinitis pigmentosa (RP). Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT), and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit), some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK. Full article
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Open AccessArticle Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions
Genes 2017, 8(7), 170; doi:10.3390/genes8070170
Received: 19 May 2017 / Revised: 20 June 2017 / Accepted: 20 June 2017 / Published: 23 June 2017
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Abstract
A significant portion of patients diagnosed with vitelliform macular dystrophy (VMD) do not carry causative mutations in the classic VMD genes BEST1 or PRPH2. We therefore performed a mutational screen in a cohort of 106 BEST1/PRPH2-negative VMD patients in two genes
[...] Read more.
A significant portion of patients diagnosed with vitelliform macular dystrophy (VMD) do not carry causative mutations in the classic VMD genes BEST1 or PRPH2. We therefore performed a mutational screen in a cohort of 106 BEST1/PRPH2-negative VMD patients in two genes encoding secreted interphotoreceptor matrix proteoglycans-1 and -2 (IMPG1 and IMPG2). We identified two novel mutations in IMPG1 in two simplex VMD cases with disease onset in their early childhood, a heterozygous p.(Leu238Pro) missense mutation and a homozygous c.807 + 5G > A splice site mutation. The latter induced partial skipping of exon 7 of IMPG1 in an in vitro splicing assay. Furthermore, we found heterozygous mutations including three stop [p.(Glu226*), p.(Ser522*), p.(Gln856*)] and five missense mutations [p.(Ala243Pro), p.(Gly1008Asp), p.(Phe1016Ser), p.(Tyr1042Cys), p.(Cys1077Phe)] in the IMPG2 gene, one of them, p.(Cys1077Phe), previously associated with VMD. Asymptomatic carriers of the p.(Ala243Pro) and p.(Cys1077Phe) mutations show subtle foveal irregularities that could characterize a subclinical stage of disease. Taken together, our results provide further evidence for an involvement of dominant and recessive mutations in IMPG1 and IMPG2 in VMD pathology. There is a remarkable similarity in the clinical appearance of mutation carriers, presenting with bilateral, central, dome-shaped foveal accumulation of yellowish material with preserved integrity of the retinal pigment epithelium (RPE). Clinical symptoms tend to be more severe for IMPG1 mutations. Full article
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Other

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Open AccessCase Report Outcome of Full-Thickness Macular Hole Surgery in Choroideremia
Genes 2017, 8(7), 187; doi:10.3390/genes8070187
Received: 29 June 2017 / Revised: 14 July 2017 / Accepted: 19 July 2017 / Published: 21 July 2017
PDF Full-text (1438 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The development of a macular hole is relatively common in retinal dystrophies eligible for gene therapy such as choroideremia. However, the subretinal delivery of gene therapy requires an uninterrupted retina to allow dispersion of the viral vector. A macular hole may thus hinder
[...] Read more.
The development of a macular hole is relatively common in retinal dystrophies eligible for gene therapy such as choroideremia. However, the subretinal delivery of gene therapy requires an uninterrupted retina to allow dispersion of the viral vector. A macular hole may thus hinder effective gene therapy. Little is known about the outcome of macular hole surgery and its possible beneficial and/or adverse effects on retinal function in patients with choroideremia. We describe a case of a unilateral full-thickness macular hole (FTMH) in a 45year-old choroideremia patient (c.1349_1349+2dup mutation in CHM gene) and its management. Pars plana vitrectomy with internal limiting membrane (ILM) peeling and 20% SF6 gas tamponade was performed, and subsequent FTMH closure was confirmed at 4 weeks, 3 months and 5 months postoperatively. No postoperative adverse events occurred, and fixation stability improved on microperimetry from respectively 11% and 44% of fixation points located within a 1° and 2° radius, preoperatively, to 94% and 100% postoperatively. This case underlines that pars plana vitrectomy with ILM peeling and gas tamponade can successfully close a FTMH in choroideremia patients, with subsequent structural and functional improvement. Macular hole closure may be important for patients to be eligible for future submacular gene therapy. Full article
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