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- Syndromic Inherited Retinal Diseases (IRD)
Syndromic Inherited Retinal Diseases (IRD) show marked differences in genetic etiology as well as clinical case presentation. They are diagnosed with sight impairment caused by defective growth, malfunctioning, or early necrosis of the retinal photoreceptors. Protheragen specializes in offering comprehensive solutions for the development of diagnostics and therapeutics tailored to address the complexities of syndromic IRDs.
Syndromic Inherited Retinal Diseases (IRDs) capture a diverse group of progressive degeneration of the retina with systemic involvement. The primary known causative factors are mutations within the genes performing various functions in the retina's operations, such as its development and maintenance. To date, more than 80 distinct syndromic forms of IRDs exist, together with nearly 200 pathogenic genes contributing to their development. The spectrum of IRDs is extensive. It includes simple cases with retinal degeneration and complex cases with multi-organ system involvement. The variability of syndromic IRDs creates immense diagnostic and therapeutic difficulties.
Fig.1 Systems and organs most commonly involved in syndromic IRDs. (Tatour Y., et al., 2020)Syndromic Inherited Retinal Diseases (IRDs) consist of two major pathways: inborn errors of metabolism or IEM and ciliopathies. IEMs have metabolic pathway defects that cause the accumulation of toxic metabolites or a lack of requisite biochemical processes that result in neurodegenerative degeneration of the retina due to its forebrain origin. Examples are the neuronal ceroid lipofuscinoses, mucopolysaccharidoses, and peroxisomal disorders. On the other hand, ciliopathies are the result of a mutation in genes that code for proteins of primary cilia, which are central to the cellular signaling of various organ systems which including development and maintenance of the retina. Bardet-Biedl Syndrome (BBS), Joubert Syndrome (JBTS), and Usher Syndrome (USH) are examples of syndromic IRDs that usually manifest with retinal degeneration, intellectual disability, renal abnormalities, and other systemic features.
Founder Mutation Screening
In some populations the existence of specific common founder mutations facilitates concentrated and streamlined genetic testing. For instance, the Ashkenazi Jewish population has high frequencies of the USH3A, USH1F, ML4 and BBS2 gene mutations, while the Finnish population exhibits higher rates of USH3A and MKS1 mutations. For this type of targeted screening DNA, PCR amplification, and Sanger sequencing are routinely performed which allows for timely and inexpensive diagnostic results. While effective, this method is restricted to populations that have documented founder mutations and is not widely applicable.
Next-Generation Sequencing (NGS)
NGS technologies have revolutionized genetic diagnosis for monogenic diseases, including IRDs. The most common NGS approaches include:
Protheragen offers comprehensive diagnostics and therapeutics development services for syndromic IRDs, leveraging cutting-edge technologies and expertise in genetic testing, gene therapy, small molecule discovery, and stem cell research. Our services are tailored to meet the unique needs of each project, ensuring rapid progress from discovery to preclinical research.
Protheragen's preclinical research services encompass a wide range of activities, including target identification and validation, high-throughput screening, lead optimization, and pharmacokinetic/pharmacodynamic (PK/PD) studies. We utilize state-of-the-art platforms and techniques to accelerate the discovery and development of novel therapeutics for syndromic IRDs. If you are interested in our services, please feel free to contact us.
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