Article
Biochemistry & Molecular Biology
Alessandro Bellapianta, Ana Cetkovic, Matthias Bolz, Ahmad Salti
Summary: Despite significant progress in modern medicine, millions of people with retinal dystrophies or age-related diseases still suffer from severe visual impairment. Reprogramming somatic cells into induced pluripotent stem cells and advancements in electronic retinal prosthesis technology offer promising opportunities for studying and treating these conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Michalis Georgiou, Naser Ali, Elizabeth Yang, Parampal S. Grewal, Tryfon Rotsos, Nikolas Pontikos, Anthony G. Robson, Michel Michaelides
Summary: This study presents detailed retinal phenotypes of patients with Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy caused by sequence variants in four genes. The findings expand the phenotypic and genotypic spectrum of these diseases, emphasizing the importance of retinal and functional phenotyping and specific genetic diagnosis for potential future therapy.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Cell Biology
Xiaodong Jiao, Zhiwei Ma, Jingqi Lei, Pinghu Liu, Xiaoyu Cai, Pawan K. Shahi, Chi-Chao Chan, Robert Fariss, Bikash R. Pattnaik, Lijin Dong, J. Fielding Hejtmancik
Summary: By constructing knockout and conditional knockout mice for KCNJ13, this study provides insights into the pathology of Snowflake Vitreoretinal Degeneration (SVD) and Retinitis pigmentosa (RP), and offers a potential model system for gene therapy trials.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vlasta Hadalin, Masa Buscarino, Jana Sajovic, Andrej Meglic, Martina Jarc-Vidmar, Marko Hawlina, Marija Volk, Ana Fakin
Summary: This study reports the genetic characteristics and long-term clinical follow-up of 18 Slovenian patients with retinitis pigmentosa GTPase regulator (RPGR) from 10 families. The results revealed known and novel variants associated with retinitis pigmentosa or cone/cone-rod dystrophy. The study provides important insights into the disease progression and visual outcomes among these patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Andrew Manley, Bahar I. Meshkat, Monica M. Jablonski, T. J. Hollingsworth
Summary: Inherited retinal dystrophies (IRDs) are congenital retinal degenerative diseases with various inheritance patterns caused by defects in retinal function, development, or both. Mutated genes associated with IRDs produce altered protein products that disrupt pathways critical to vision. This manuscript provides a comprehensive review of the molecular mechanisms underlying IRD pathogenesis by examining the genes, protein products, and pathways affected by genetic mutation.
Article
Ophthalmology
Katie M. Williams, Michalis Georgiou, Angelos Kalitzeos, Isabelle Chow, Pirro G. Hysi, Anthony G. Robson, Gareth Lingham, Fred K. Chen, David A. Mackey, Andrew R. Webster, Christopher J. Hammond, Polina Prokhoda, Joseph Carroll, Michel Michaelides, Omar A. Mahroo
Summary: This study investigates the axial length distributions in inherited retinal diseases (IRDs) and compares them with reference cohorts. The findings suggest that some IRDs are associated with longer axial lengths, while others are associated with shorter axial lengths.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Ophthalmology
Gernot Schliessleder, Angelos Kalitzeos, Melissa Kasilian, Navjit Singh, Ziyuan Wang, Zhihong Hu, Manuel Grosspoetzl, SriniVas Sadda, Andreas Wedrich, Michel Michaelides, Rupert W. Strauss
Summary: This study aimed to investigate the retinal structure in patients with autosomal-dominant and autosomal-recessive PROM1-associated retinal degeneration. Ophthalmic examination and multimodal retinal imaging revealed atrophic lesions, thinning of the outer retinal layers, and variations in cone photoreceptor quantification, which were related to disease-causing variants and age.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Ophthalmology
Laryssa A. Huryn, Christina Torres Kozycki, Jasmine Y. Serpen, Wadih M. Zein, Ehsan Ullah, Alessandro Iannaccone, Lloyd B. Williams, Lucia Sobrin, Brian P. Brooks, H. Nida Sen, Robert B. Hufnagel, Daniel L. Kastner, Shilpa Kodati
Summary: The purpose of this study was to characterize the ocular phenotype of patients with ROSAH syndrome and their response to therapy. Patients with molecularly confirmed ROSAH syndrome were evaluated and it was found that optic nerve involvement, intraocular inflammation, and retinal degeneration were the main factors contributing to changes in visual function of patients with ROSAH syndrome.
Article
Ophthalmology
Maria della Volpe Waizel, Hendrik P. N. Scholl, Christophe Valmaggia, Margarita G. Todorova
Summary: This study found that children with inherited retinal diseases show early metabolic changes, especially those with rod-cone dystrophy (RCD) being more affected. Retinal vessel oximetry may support early screening and differentiation of RCD in children.
ACTA OPHTHALMOLOGICA
(2021)
Review
Ophthalmology
Malena Daich Varela, Burak Esener, Shaima A. Hashem, Thales Antonio Cabral de Guimaraes, Michalis Georgiou, Michel Michaelides
Summary: Ophthalmic genetics has rapidly evolved in the past decade, particularly in translational medicine for inherited retinal diseases. This review discusses various methods for objectively and accurately assessing retinal structure in IRD patients, including standard imaging techniques and newer technologies, showing their utility in ongoing therapeutic efforts/trials.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Genetics & Heredity
Jin Kyun Oh, Jose G. Vargas Del Valle, Jose Ronaldo Lima de Carvalho, Young Joo Sun, Sarah R. Levi, Joseph Ryu, Jing Yang, Takayuki Nagasaki, Andres Emanuelli, Nailyn Rasool, Rando Allikmets, Janet R. Sparrow, Natalio J. Izquierdo, Jacque L. Duncan, Vinit B. Mahajan, Stephen H. Tsang
Summary: This study describes the phenotypic findings in three unrelated patients with novel mutations in TTLL5, expanding the understanding of TTLL5-mediated retinal disease. The study suggests that mutations in TTLL5 may not only cause cone-rod and cone dystrophies, but also sectoral retinal dystrophy.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Julia Zhu, Kirk A. J. Stephenson, Adrian Dockery, Jacqueline Turner, James J. O'Byrne, Susan Fitzsimon, G. Jane Farrar, D. Ian Flitcroft, David J. Keegan
Summary: Inherited retinal degenerations (IRDs) account for a significant proportion of pediatric blindness, and there are often long delays in reaching a diagnosis. In this study, a telegenetics approach was used to offer genetic testing to children with phenotypic evidence of IRD during the COVID-19 pandemic. Genetic testing identified causative genetic variants in a high percentage of patients, and a significant proportion were eligible for approved therapies or clinical trial-based gene therapies. Early introduction of genetic testing is crucial for genetic counseling and preparation for upcoming gene therapy trials in pediatric IRD patients.
Article
Biochemistry & Molecular Biology
Andrea Stofkova, Miloslav Zloh, Dominika Andreanska, Ivana Fiserova, Jan Kubovciak, Jan Hejda, Patrik Kutilek, Masaaki Murakami
Summary: This study demonstrates that the dysfunction of rod photoreceptors leads to the development of autoimmune uveitis. Dopamine mediates the control of immune cell entry into the retina by inhibiting NF-kappa B and STAT3 activity and the expression of chemokines involved in T cell recruitment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Tess A. V. Afanasyeva, Dimitra Athanasiou, Pedro R. L. Perdigao, Kae R. Whiting, Lonneke Duijkers, Galuh D. N. Astuti, Jean Bennett, Alejandro Garanto, Jacqueline van der Spuy, Ronald Roepman, Michael E. Cheetham, Rob W. J. Collin
Summary: In this study, a patient-specific cellular model of LCA5-associated retinal disease was generated by correcting a mutation in the LCA5 gene using CRISPR-Cas9 technology. The absence of off-target editing was confirmed in the gene-corrected cells through whole-genome sequencing. Three-dimensional retinal organoids derived from patient cells, gene-corrected cells, and unrelated control cells were used to observe the mislocalization of opsin and rhodopsin in patient cells and the rescue of lebercilin expression and localization in gene-corrected cells. This study demonstrates the potential of combining precise gene editing with iPSC-derived retinal organoids for modeling early-onset retinal diseases.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Genetics & Heredity
Leo H. N. Sheck, Simona D. Esposti, Omar A. Mahroo, Gavin Arno, Nikolas Pontikos, Genevieve Wright, Andrew R. Webster, Kamron N. Khan, Michel Michaelides
Summary: This study demonstrates that NGS 176 panel-based genetic testing is a useful tool for diagnosing patients with inherited retinal diseases, with age and initial clinical diagnosis strongly associated with diagnostic yield.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Editorial Material
Ophthalmology
Bernhard Lachenmayr, Gernot Freissler, Siegfried Drosch, Joerg Frischmuth, Klaus Rohrschneider, Johann Roider, Frank Tost, Helmut Wilhelm
Article
Ophthalmology
Andreas Viberg, Ida Maria Westin, Irina Golovleva, Berit Bystrom
Summary: In northern Sweden, almost 90% of FECD patients have a (CTG)(n) repeat expansion in the TCF4 gene, with repeat length being associated with disease severity. Additionally, FECD cases without a TCF4 repeat expansion have a higher rate of ocular surgery compared to those with a repeat expansion.
ACTA OPHTHALMOLOGICA
(2022)
Article
Biochemistry & Molecular Biology
Katarina Stingl, Britta Baumann, Pietro De Angeli, Ajoy Vincent, Elise Heon, Monique Cordonnier, Elfriede De Baere, Salmo Raskin, Mario Teruo Sato, Naoye Shiokawa, Susanne Kohl, Bernd Wissinger
Summary: Certain combinations of variants in exon 3 of OPN1LW and OPN1MW induce splicing defects and are associated with visual disorders. A novel exon 3 haplotype with a splicing defect has been identified in patients with cone dysfunction. The patients carrying this haplotype showed symptoms of Blue Cone Monochromacy or Bornholm Eye Disease with reduced visual acuity and color vision defects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Rebekkah J. Hitti-Malin, Claire-Marie Dhaenens, Daan M. Panneman, Zelia Corradi, Mubeen Khan, Anneke den Hollander, G. Jane Farrar, Christian Gilissen, Alexander Hoischen, Maartje van de Vorst, Femke Bults, Erica G. M. Boonen, Patrick Saunders, Md Study Group, Susanne Roosing, Frans P. M. Cremers
Summary: Macular degenerations (MDs), a subgroup of retinal disorders, are characterized by central vision loss. This study used smMIPs sequencing to investigate the genetic factors influencing MDs and identified new variants and genetic associations.
Review
Pathology
Alessandro Pietro Aldera, Komala Pillay, Barbara Robertson, Adam Boutall, Rajkumar Ramesar
Summary: Our understanding of the molecular classification of colorectal carcinoma has significantly evolved in the past two decades. However, most of the data on which this classification is based come from Europe and North America, with limited representation from Africa. Preliminary studies have shown significant differences in molecular characteristics between African and other populations, suggesting the need for further research.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Oncology
Yasmina Johnson, Paul Goldberg, Jennifer Moodley, Ursula Algar, Sandie Thomson, Edina Sinanovic, Raj Ramesar
Summary: This study compared the cost of two strategies for colonoscopy screening of relatives of Lynch Syndrome patients in a resource-constrained healthcare system. The results showed that combining genetic analysis with colonoscopy screening resulted in a 92% reduction in cost compared to colonoscopy screening alone.
CANCER CAUSES & CONTROL
(2023)
Article
Genetics & Heredity
Netasha Khan, Andrew D. Paterson, Delnaz Roshandel, Saadia Maqbool, Nosheen Fazal, Liaqat Ali, Raja Khurram, Sundus Ijaz Maqsood, Syeda Hafiza Benish Ali, Hira Khan, Khadija Tariq, Saira Bano, Aisha Azam, Irfan Muslim, Maleeha Maria, Zehra Agha, Mujtaba Babar, Nadia Khalida Waheed, Maleeha Azam, Raheel Qamar
Summary: This study evaluated the genetic association of 10 loci with type 2 diabetes (T2D), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) in the Pakistani population. In multivariate analysis, it was found that several loci were associated with a higher risk of T2D and PDR.
Article
Genetics & Heredity
Alina I. Esterhuizen, Nicki Tiffin, Gillian Riordan, Marie Wessels, Richard J. Burman, Miriam C. Aziz, Jeffrey D. Calhoun, Jonathan Gunti, Ezra E. Amiri, Aishwarya Ramamurthy, Michael J. Bamshad, Heather C. Mefford, Raj Ramesar, Jo M. Wilmshurst, Gemma L. Carvill
Summary: This study aims to improve awareness and testing options for epilepsy in Sub-Saharan Africa. By using genetic testing, researchers identified genes associated with developmental and epileptic encephalopathies (DEEs) and proposed a strategy for early recognition of potential genetic causes.
GENETICS IN MEDICINE
(2023)
Article
Medicine, General & Internal
Iulia Potorac, Marie Laterre, Olivier Malaise, Vlad Nechifor, Corinne Fasquelle, Orphal Colleye, Nancy Detrembleur, Hannah Verdin, Sofie Symoens, Elfride De Baere, Adrian F. Daly, Vincent Bours, Patrick Petrossians, Axelle Pintiaux
Summary: Infertility is a common problem in couples, with both female and male factors playing a similar role. Rare congenital disorders can affect both female and male gametogenesis. Mutations in the MCM9 gene have been found to cause premature ovarian insufficiency in females and are also associated with an increased risk of cancer.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cell Biology
Ramadhani Chambuso, Mbali Mthembu, Eveline Kaambo, Barbara Robertson, Raj Ramesar
Summary: Lynch syndrome is a hereditary disorder with increased risk of colorectal and non-colorectal cancers. Mutations in DNA repair genes lead to dysfunctional post-replication repair system and production of neoantigens, triggering an immune response. Due to invasive nature of screening tests, adherence to cancer screening guidelines among Lynch variant heterozygotes is poor. The potential of immunogenomic biomarkers in Lynch syndrome and their correlation with cancer onset and stage is currently unclear.
Article
Cardiac & Cardiovascular Systems
Tafadzwa Machipisa, Chishala Chishala, Gasnat Shaboodien, Liesl J. Zuhlke, Babu Muhamed, Shahiemah Pandie, Jantina de Vries, Nakita Laing, Alexia Joachim, Rezeen Daniels, Mpiko Ntsekhe, Christopher T. Hugo-Hamman, Bernard Gitura, Stephen Ogendo, Peter Lwabi, Emmy Okello, Albertino Damasceno, Celia Novela, Ana O. Mocumbi, Geoffrey Madeira, John Musuku, Agnes Mtaja, Ahmed ElSayed, Huda H. M. Alhassan, Fidelia Bode-Thomas, Christopher Yilgwan, Ganiyu Amusa, Esin Nkereuwem, Nicola Mulder, Raj Ramesar, Maia Lesosky, Heather J. Cordell, Michael Chong, Bernard Keavney, Guillaume Pare, Mark E. Engel
Summary: The RHDGen Network aims to discover and validate genetic variations and biomarkers associated with the risk of rheumatic heart disease (RHD) in continental Africans. The study provides an opportunity to identify relevant genetic factors and biomarkers for RHD in Africans and further understand the causes and mechanisms of RHD susceptibility and development.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Ida Maria Westin, Mattias Landfors, Antonios Giannopoulos, Andreas Viberg, Pia Osterman, Berit Bystrom, Sofie Degerman, Irina Golovleva
Summary: Late-onset Fuchs endothelial corneal dystrophy (FECD) is associated with CTG18.1 expansions in the TCF4 gene, causing specific methylation changes in corneal endothelium. Gene expression analysis showed altered expression of AQP1, F5, and THBD in FECD, while age-dependent hypomethylation was observed in healthy corneal endothelium.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Farhan Khashim Alswailmi, Rida Khursheed Malik, Mujeeb Ur Rehman Parrey, Abdul Rauf Siddiqi, Shaik Karimulla, Abdulkareem A. Alanezi, Raheel Qamar, Maleeha Azam, Ashfaq Ahmad
Summary: This study investigated the role of VSX1 in the development of KC in Pakistani families and sporadic patients. Rare genetic variations in VSX1 were found, and two single nucleotide polymorphisms were identified as potentially contributing to KC development by affecting the identification of cis-acting elements and binding motifs for microRNAs.
APPLIED SCIENCES-BASEL
(2023)
Article
Medicine, Research & Experimental
Melita Kaltak, Rocio Blanco-Garavito, Laurie L. Molday, Claire-Marie Dhaenens, Eric E. Souied, Gerard Platenburg, Jim Swildens, Robert S. Molday, Frans P. M. Cremers
Summary: This study investigated the exon skipping phenomenon of exon 17 in the ABCA4 gene associated with Stargardt disease (STGD1) and designed corresponding oligonucleotides to induce exon 17 skipping. The results showed that the deletion of exon 17 in ABCA4 does not result in the absence of protein activity and does not cause a severe STGD1 phenotype when in trans with a null allele. Therefore, the impact of severe variants in exon 17 can potentially be ameliorated by exon skipping using antisense oligonucleotides (AONs), generating partial ABCA4 activity in STGD1 patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Proceedings Paper
Computer Science, Interdisciplinary Applications
Raj Ramesar, Ramadhani Chambuso
Summary: This paper describes a programme focused on identifying familial colorectal cancers, particularly Lynch syndrome, and the use of implementation science. The programme involves genetic testing, counseling, cascade screening, and surveillance colonoscopies conducted by a multidisciplinary team. The paper highlights the economic benefits and value of using this proven precision medicine programme to address inherited cancers in Africa. The combination of selected next-generation DNA sequencing technologies, targeted implementation science programs, skilled multidisciplinary teams, and patient involvement can significantly reduce the incidence, survival, and health-economic impact of Lynch syndrome and other familial colorectal cancers.
2022 IST-AFRICA CONFERENCE
(2022)