Non-coding RNAs in retinal development and function

Abstract

Accumulating evidence on the role of non-protein-coding RNA sequences in the regulation of gene expression is greatly expanding our understanding of the flow of genetic information within biological systems. The interplay between protein-coding and non-coding RNAs (ncRNAs) is essential for tissue development, homeostasis, and function. NcRNAs can be divided in short ncRNAs, whose main subtype is represented by microRNAs, and long ncRNAs, which constitute a more heterogeneous class. The retina is a light-sensitive tissue consisting of highly interconnected cell types and is the primary target of many genetic diseases. Among these, the genetically heterogeneous group of inherited retinal diseases (IRDs) represents the most frequent monogenic cause of visual impairment that can ultimately lead to blindness. Here, we provide an overview on the role of ncRNAs in retinal development and function with an emphasis on microRNAs and on different types of long ncRNAs. We also review how sequence variations in ncRNAs can play a pathogenic role in IRDs as well as in multifactorial ocular disorders. These data indicate that a comprehensive study of the contribution of ncRNAs to the mutation repertoire associated with retinal disease can shed light on previously unknown pathophysiological mechanisms and open new therapeutic avenues. We conclude that a more comprehensive dissection of the pathogenic role of non-coding RNAs in retinal function and disease will not only improve our diagnostic ability, but will allow the development of novel targeted therapies for ocular disease.

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Bicuspid Aortic Valve: Role of Multiple Gene Variants in Influencing the Clinical Phenotype

Background. Bicuspid aortic valve (BAV) is a common congenital heart defect with increased prevalence of aortic dilatation and dissection. BAV has an autosomal dominant pattern of inheritance with reduced penetrance and variable expressivity. BAV has been described as an isolated trait or associated with other clinical manifestations in syndromic conditions. Identification of a syndromic condition in a BAV patient is clinically relevant in order to personalize indication to aortic surgery. We aimed to point out how genetic diagnosis by next-generation sequencing (NGS) can improve management of a patient with complex BAV clinical picture. Methods and Results. We describe a 45-year-old Caucasian male with BAV, thoracic aortic root and ascending aorta dilatation, and connective features evocative but inconclusive for clinical diagnosis of Marfan syndrome (MFS). Targeted (91 genes) NGS was used. Proband genetic variants were investigated in first-degree relatives. Proband carried 5 rare variants in 4 genes: FBN1(p.Asn542Ser and p.Lys2460Arg), NOTCH1(p.Val1739Met), LTBP1(p.Arg1330Gln), and TGFBR3(p.Arg423Trp). The two FBN1 variants were inherited in cis by the mother, showing systemic features evocative of MFS, but with a milder phenotype than that observed in the proband. Careful clinical observation along with the presence of the FBN1 variants allowed diagnosis of MFS in the proband and in his mother. NOTCH1 variant was found in mother and brother, not exhibiting BAV, thus not definitely supporting/excluding association with BAV. Interestingly, the proband, his brother and father, all showing root dilatation, and his sister, with upper range aortic root dimension, were carriers of a TGFBR3 variant. LTBP1 might also modulate the vascular phenotype. Conclusions. Our results underline the usefulness of NGS together with family evaluation in diagnosis of patients with monogenic traits and overlapping clinical manifestations due to contribution of the same genes and/or presence of comorbidities determined by different genes.

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Recent Advances of Optical Imaging in the Second Near‐Infrared Window

Advanced Materials, EarlyView.


https://ift.tt/2PFXA8a

Enhanced Thermal Boundary Conductance in Few‐Layer Ti3C2 MXene with Encapsulation

Advanced Materials, EarlyView.


https://ift.tt/2MMFeW2

Enhancing the n‐Type Conductivity and Thermoelectric Performance of Donor–Acceptor Copolymers through Donor Engineering

Advanced Materials, EarlyView.


https://ift.tt/2LXuBua

Lack of response to quinidine in KCNT1‐related neonatal epilepsy

Epilepsia, EarlyView.


https://ift.tt/2wNVUlP

Antivirals in Combination with Corticosteroids for the Treatment of Acute Bell's Palsy

Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Ctgops