Inherited Macular Dystrophies and Differential Diagnostics

Liutkevičienė, Rasa; Lesauskaitė, Vaiva; Ašmonienė, Virginija; Gelžinis, Arvydas; Žaliūnienė, Dalia; Jašinskas, Vytautas

doi:10.3390/medicina48090072

Cited by 6 publications

(6 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our patient’s phenotype was consistent with Stargardt disease (8). Genetic testing revealed novel compound heterozygous ABCA4 deletions, c.850_857delATTCAAGA and c.6184_6187delGTCT.…”

Section: Discussionsupporting

confidence: 75%

Novel ABCA4 mutation leads to loss of a conserved C-terminal motif: implications for predicting pathogenicity based on genetic testing

Wangtiraumnuay

Capasso

Tsukikawa

et al. 2018

European Journal of Ophthalmology

View full text Add to dashboard Cite

Genotyping microarray chips for ABCA4 can identify >98% of the most common mutations. DNA sequencing may identify novel variants with uncertain significance or lack of consensus regarding pathogenicity. Mutations in other genes may result in Stargardt disease phenocopies (3). An ABCA4 sequence variant can therefore not be presumed to cause the patient's phenotype. Understanding the functional implications of genetic variants at the protein level can allow prediction of protein loss of function or toxic gain of function. In this report, we describe 2 novel ABCA4 variants in a patient with Stargardt disease. Bioinformatic and in silico analysis of the functional consequences of these variants provided compelling evidence for pathogenicity.

show abstract

“…Our patient’s phenotype was consistent with Stargardt disease (8). Genetic testing revealed novel compound heterozygous ABCA4 deletions, c.850_857delATTCAAGA and c.6184_6187delGTCT.…”

Section: Discussionsupporting

confidence: 75%

Novel ABCA4 mutation leads to loss of a conserved C-terminal motif: implications for predicting pathogenicity based on genetic testing

Wangtiraumnuay

Capasso

Tsukikawa

et al. 2018

European Journal of Ophthalmology

View full text Add to dashboard Cite

show abstract

“…Many ocular diseases tend to affect the macula. These diseases are usually degenerative diseases that cause neuronal loss and, thus, produce the thickness of the total macula and cause different macular layers to thin [ 3 , 4 , 5 ]. However, some other diseases also produce increased thickness of macular layers [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Normative Database for All Retinal Layer Thicknesses Using SD-OCT Posterior Pole Algorithm and the Effects of Age, Gender and Axial Lenght

Palazón-Cabanes

Rubio-Velázquez

et al. 2020

JCM

View full text Add to dashboard Cite

Our aim was to provide, for the first time, reference thickness values for the SD-OCT posterior pole algorithm (PPA) available for Spectralis OCT device (Heidelberg Engineering, Heidelberg, Germany) and to analyze the correlations with age, gender and axial length. We recruited 300 eyes of 300 healthy Caucasian subjects between 18 and 84 years. By PPA, composed of 64 (8 × 8) cells, we analyzed the thickness of the following macular layers: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), inner retina, outer retina and full retina. Mean ± SD, 1st, 5th, 95th percentiles were obtained for each cell at all macular layers. Significant negative correlations were found between age and thickness for most macular layers. The mean thickness of most macular layers was thicker for men than women, except for RNFL, OPL and RPE, with no gender differences. GCL, IPL and INL thicknesses positively correlated with axial length in central cells, and negatively in the cells near the optic disk. The mean RNFL thickness was positively associated with axial length. This is the first normative database for PPA. Age, gender and axial length should be taken into account when interpreting PPA results.

show abstract

“…Retinal dystrophies are categorized roughly into two categories: 1) retinitis pigmentosa (RP), a broad term encompassing phenotypes that initially affect rod photoreceptors and peripheral vision, and may later be associated with cone cell death, and 2) macular dystrophy (MD), a term encompassing widely varying phenotypes in which macular or central vision is initially affected(2, 3). Though MD can be caused by defects in cone photoreceptors, it can also be caused by defects in the retinal pigment epithelium (RPE).…”

Section: Introductionmentioning

confidence: 99%

Non-viral therapeutic approaches to ocular diseases: An overview and future directions

Zulliger

Conley

Naash

2015

Journal of Controlled Release

View full text Add to dashboard Cite

Currently there are no viable treatment options for patients with debilitating inherited retinal degeneration. The vast variability in disease-inducing mutations and resulting phenotypes has hampered the development of therapeutic interventions. Gene therapy is a logical approach, and recent work has focused on ways to optimize vector design and packaging to promote optimized expression and phenotypic rescue after intraocular delivery. In this review, we discuss ongoing ocular clinical trials, which currently use viral gene delivery, but focus primarily on new advancements in optimizing the efficacy of non-viral gene delivery for ocular diseases. Non-viral delivery systems are highly customizable, allowing functionalization to improve cellular and nuclear uptake, bypassing cellular degradative machinery, and improving gene expression in the nucleus. Non-viral vectors often yield transgene expression levels lower than viral counterparts, however their favorable safety/immune profiles and large DNA capacity (critical for the delivery of large ocular disease genes) make their further development a research priority. Recent work on particle coating and vector engineering present exciting ways to overcome limitations of transient/low gene expression levels, but also highlight the fact that further refinements are needed before use in the clinic.

show abstract

Inherited Macular Dystrophies and Differential Diagnostics

Cited by 6 publications

References 52 publications

Novel ABCA4 mutation leads to loss of a conserved C-terminal motif: implications for predicting pathogenicity based on genetic testing

Novel ABCA4 mutation leads to loss of a conserved C-terminal motif: implications for predicting pathogenicity based on genetic testing

Normative Database for All Retinal Layer Thicknesses Using SD-OCT Posterior Pole Algorithm and the Effects of Age, Gender and Axial Lenght

Non-viral therapeutic approaches to ocular diseases: An overview and future directions

Contact Info

Product

Resources

About