Article
Genetics & Heredity
Isabelle Perrault, Sylvain Hanein, Xavier Gerard, Nelson Mounguengue, Ryme Bouyakoub, Mohammed Zarhrate, Cecile Fourrage, Fabienne Jabot-Hanin, Beatrice Bocquet, Isabelle Meunier, Xavier Zanlonghi, Josseline Kaplan, Jean-Michel Rozet
Summary: This study investigates the non-coding regions of a non-syndromic LCA gene, identifying the most frequent disease allele.
Article
Genetics & Heredity
Amani Albakri, Phattrawan Pisuchpen, Jenina E. Capasso, Adele Schneider, Sarina Kopinsky, Tom Glaser, John P. -W. Chiang, Anamaria Akapito Yomai, Donna McNear, Alex V. Levin
Summary: The purpose of this article is to determine the cause of Leber congenital amaurosis (LCA) in Chuuk state, Federated States of Micronesia (FSM). Five patients with early-onset vision loss were examined in Chuuk state, FSM, and were initially misdiagnosed with microphthalmia. However, a complete ophthalmological exam established a clinical diagnosis of LCA. DNA sequencing revealed a homozygous CRB1 NM_201253.3:c.3134del pathogenic variant in affected individuals. This discovery of a founder pathogenic variant in CRB1 will lead to appropriate recurrence risk counseling.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Genetics & Heredity
Wenhua Duan, Taicheng Zhou, Huawei Jiang, Minhui Zhang, Min Hu, Liwei Zhang
Summary: This study identified a novel variant in the CRB1 gene in a Chinese family with LCA, expanding the spectrum of CRB1 variants causing LCA.
BMC MEDICAL GENOMICS
(2022)
Article
Ophthalmology
Xufeng Dai, Xumin Jin, Qian Ye, Haixiao Huang, Lan Duo, Chunjie Lu, Jinhua Bao, Hao Chen
Summary: High expression of the RPE-specific RPE65 enzyme is crucial for generating 11-cis-retinal, a key component for vision. Deficiency in RPE65 can lead to severe retinal dysfunction, but early treatment with 11-cis-retinal in a mouse model shows promise in delaying cone degeneration and preserving retinal function.
EXPERIMENTAL EYE RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Wei Chiu, Ting-Yi Lin, Yun-Chia Chang, Henkie Isahwan-Ahmad Mulyadi Lai, Shen-Che Lin, Chun Ma, Aliaksandr A. Yarmishyn, Shiuan-Chen Lin, Kao-Jung Chang, Yu-Bai Chou, Chih-Chien Hsu, Tai-Chi Lin, Shih-Jen Chen, Yueh Chien, Yi-Ping Yang, De-Kuang Hwang
Summary: Inherited retinal dystrophies (IRDs) are rare eye diseases caused by gene mutations, and gene therapy has shown promising prospects in treating these diseases. Gene therapy for patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) has been approved by the FDA, marking a significant advancement in the field of genetic treatments for eye diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Anatomy & Morphology
Ankur Nahar, Seo-Hee Cho
Summary: Mutations in the CRB1 gene cause rare retinal diseases like RP12 and LCA8. While several mouse models have been proposed for RP12, few replicate the full spectrum of human LCA8 pathology. LCA8 is a unique type of retinal dystrophy driven by dysfunctional retinal progenitor cells, while other LCA subtypes and RP12 are caused by photoreceptor defects. Therefore, the most accurate LCA8-like mouse model should target both Crb1 and Crb2 genes in the early stages of eye development.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Genetics & Heredity
Tomas S. Aleman, Erin C. O'Neil, Katherine E. Uyhazi, Kelsey M. Parchinski, Arlene J. Santos, Mariejel L. Weber, Sherice P. Colclough, Andrew S. Billek, Xiaosong Zhu, Bart P. Leroy, Emma C. Bedoukian
Summary: This study retrospectively reviewed the ophthalmic phenotype of five patients with CEP290-LCA. Patients displayed relative structural preservation in the foveal and near midperipheral retina, with photoreceptor loss in the pericentral area. Yellow-white, fleck-like lesions co-localized with hyperreflective lesions on SD-OCT, located between the inner segment ellipsoid signal and the apical RPE.
OPHTHALMIC GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Ditta Zobor, Britta Bruehwiler, Eberhart Zrenner, Nicole Weisschuh, Susanne Kohl
Summary: This study investigates the spectrum of LCA-associated genes in a large German cohort, providing valuable insights into the genetic and phenotypic diversity of LCA. The results indicate the importance of genetic information in gene therapeutic trials for LCA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Ophthalmology
Sriee Viswarubhiny, Rupa Anjanamurthy, Ayyasamy Vanniarajan, Devarajan Bharanidharan, Vijayalakshmi Perumalsamy, Periasamy Sundaresan
Summary: This study identified causative mutations in nine LCA patients through clinical exome sequencing, reporting novel mutations in PRPH2, CEP290, and ALMS1 in the Indian population, and observed a novel association of LCA phenotype with Jeune syndrome.
Article
Genetics & Heredity
Shijing Wu, Zhisheng Yuan, Zixi Sun, Fengxia Yao, Ruifang Sui
Summary: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is an autosomal recessive disorder caused by a defective SLC19A2 gene, with characteristic triad manifestations of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Ophthalmic features such as retinitis pigmentosa and optic atrophy can also be present. This case illustrates that Leber congenital amaurosis may precede systemic manifestations in TRMA patients.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Biochemistry & Molecular Biology
Maximilian J. Gerhardt, Claudia S. Priglinger, Guenther Rudolph, Karsten Hufendiek, Carsten Framme, Herbert Jaegle, Daniel J. Salchow, Andreas Anschuetz, Stylianos Michalakis, Siegfried G. Priglinger
Summary: This study presented the follow-up of the youngest treated patients in Germany with Leber congenital amaurosis caused by mutations in the RPE65 gene. The results showed significant improvement in vision and electrophysiological recovery in some patients after treatment with voretigene neparvovec gene therapy. These findings highlight the positive role of voretigene neparvovec in treating this devastating eye disease.
Article
Biochemistry & Molecular Biology
Samagya Banskota, Aditya Raguram, Susie Suh, Samuel W. Du, Jessie R. Davis, Elliot H. Choi, Xiao Wang, Sarah C. Nielsen, Gregory A. Newby, Peyton B. Randolph, Mark J. Osborn, Kiran Musunuru, Krzysztof Palczewski, David R. Liu
Summary: We have developed and applied engineered DNA-free virus-like particles (eVLPs) for efficient delivery of gene editing tools, achieving high levels of base editing. By overcoming the limitations of cargo packaging, release, and localization, the fourth-generation eVLPs demonstrated efficient base editing in mouse and human cells. In addition, the off-target effects of eVLPs were significantly reduced compared to other delivery methods such as AAV or plasmid.
Article
Ophthalmology
M. Dominik Fischer, Francesco Patalano, Christel Naujoks, Judit Banhazi, Christine Bouchet, Paul O'Brien, Christine Kay, Jane Green, Todd Durham, Helena Bradley, Nicola Williamson, Melissa Barclay, Joel Sims, Isabelle Audo
Summary: This study explores the psychometric properties of the ViSIO-PRO and ViSIO-ObsRO instruments in RP/LCA. The findings suggest that the questionnaires are reliable and valid measures in RP/LCA, and further research is needed to examine their responsiveness and interpretation of change scores.
OPHTHALMOLOGY AND THERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Alaknanda Mishra, Camasamudram Vijayasarathy, Catherine A. Cukras, Henry E. Wiley, H. Nida Sen, Yong Zeng, Lisa L. Wei, Paul A. Sieving
Summary: This study revealed that patients with XLRS may have a proinflammatory baseline immune phenotype, and intravitreal dosing with AAV8-RS1 leads to systemic immune activation characterized by an increase in activated lymphocytes, macrophages, and proinflammatory cytokines.
Review
Ophthalmology
Bart P. Leroy, David G. Birch, Jacque L. Duncan, Byron L. Lam, Robert K. Koenekoop, Fernanda B. O. Porto, Stephen R. Russell, Aniz Girach
Summary: LCA10, caused by CEP290 mutations, is a genetic retinal disease leading to severe visual impairment in early childhood. There are currently no approved treatments, but investigational strategies include RNA editing using antisense oligonucleotides or CRISPR-based approaches. The antisense oligonucleotide therapy QR-110 has shown promising results in early trials, with ongoing phase 3 clinical trials.
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
(2021)
Review
Genetics & Heredity
M. Stemerdink, B. Garcia-Bohorquez, R. Schellens, G. Garcia-Garcia, E. Van Wijk, J. M. Millan
Summary: Usher syndrome is a rare genetic disorder characterized by sensory neural hearing loss and progressive vision loss. Research indicates that sleep deprivation, olfactory dysfunction, and other symptoms are also part of the disease. Genetic and clinical research, as well as therapeutic approaches for Usher syndrome, are currently being developed to potentially provide treatment for patients.
Article
Genetics & Heredity
Hannie Kremer
Summary: Despite decades of research, there is still much to be explored in the genetic landscape of sensorineural hearing loss. Finding new genes and uncovering the 'secrets' of known genes are essential for improving genetic diagnostics and developing therapeutic strategies. Collaborative studies and maximizing the use of available tools and resources are crucial for accelerating these discoveries.
Review
Biochemistry & Molecular Biology
Sybren M. M. Robijn, Jeroen J. Smits, Kadriye Sezer, Patrick L. M. Huygen, Andy J. Beynon, Erwin van Wijk, Hannie Kremer, Erik de Vrieze, Cornelis P. Lanting, Ronald J. E. Pennings
Summary: This study provides a comprehensive overview of genotype-phenotype correlations in COCH gene variants associated with DFNA9. Analysis of 48 studies reveals a highly variable audiovestibular phenotype in DFNA9, with variants affecting the LCCL domain of cochlin generally leading to more severe hearing loss.
Article
Anatomy & Morphology
Sarah M. Kamel, Sanne Broekman, Federico Tessadori, Erwin van Wijk, Jeroen Bakkers
Summary: This study demonstrates the importance of Sgo1 in organ development and function using a zebrafish model, and reveals that its mutation may lead to abnormal cardiac function, impaired vision, and reduced food intake.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Ailis L. Moran, Stephen P. Carter, Joanna J. Kaylor, Zhichun Jiang, Sanne Broekman, Eugene T. Dillon, Alicia Gomez Sanchez, Sajal K. Minhas, Erwin van Wijk, Roxana A. Radu, Gabriel H. Travis, Michelle Carey, Oliver E. Blacque, Breandan N. Kennedy
Summary: The study reveals the importance of Rab28 in regulating both dawn and dusk peaks of outer segment phagocytosis (OSP). Loss of Rab28 leads to dysregulation of factors associated with OSP and perturbs the visual cycle. Transgenic overexpression of Rab28 in zebrafish cones rescues the OSP defect, highlighting the role of Rab28 in regulating OSP.
Article
Audiology & Speech-Language Pathology
Katelyn N. Robillard, Erik de Vrieze, Erwin van Wijk, Jennifer J. Lentz
Summary: Hearing loss, affecting over 430 million people worldwide, has significant impacts on physical, cognitive, and overall well-being. Antisense oligonucleotide (ASO)-based therapies show promise in treating hereditary hearing loss disorders by manipulating gene expression and targeting specific genetic factors.
Editorial Material
Genetics & Heredity
Hannie Kremer, Ignacio del Castillo
Article
Biochemical Research Methods
R. T. W. Schellens, R. W. N. Slijkerman, L. Hetterschijt, T. A. Peters, S. Broekman, A. Clement, M. Westerfield, J. B. Phillips, K. Boldt, H. Kremer, E. De Vrieze, E. Van Wijk
Summary: In this study, whirlin-associated protein complexes were isolated and characterized from zebrafish photoreceptor cells. 19 novel candidate associated proteins were identified, and the association of 7 proteins with WHRN was confirmed. These findings suggest a role for whirlin in the photoreceptor synapse and provide insight into the molecular pathogenesis of Usher syndrome type 2.
JOURNAL OF PROTEOMICS
(2022)
Article
Genetics & Heredity
Janine Reurink, Erik de Vrieze, Catherina H. Z. Li, Emma van Berkel, Sanne Broekman, Marco Aben, Theo Peters, Jaap Oostrik, Kornelia Neveling, Hanka Venselaar, Mariana Guimaraes Ramos, Christian Gilissen, Galuh D. N. Astuti, Jordi Corominas Galbany, Janneke J. C. van Lith-Verhoeven, Charlotte W. Ockeloen, Lonneke Haer-Wigman, Carel B. Hoyng, Frans P. M. Cremers, Hannie Kremer, Susanne Roosing, Erwin van Wijk
Summary: The pathogenicity of the USH2A c.2276 G > T variant as a common cause of autosomal recessive retinitis pigmentosa was confirmed through genetic and functional analyses. A zebrafish model was generated to validate the findings. This study has significant implications for genetic diagnosis and future treatment options for this disease.
NPJ GENOMIC MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Janine Reurink, Jaap Oostrik, Marco Aben, Mariana Guimaraes Ramos, Emma van Berkel, Monika Oldak, Erwin van Wijk, Hannie Kremer, Susanne Roosing, Frans P. M. Cremers
Summary: This study aimed to expand the understanding of splicing events and assess a selected set of non-canonical splice site variants in USH2A. The results showed that these variants had an effect on pre-mRNA splicing, highlighting their significance in the genetic etiology of associated disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Hedwig M. M. Velde, Xanne J. J. Huizenga, Helger G. G. Yntema, Lonneke Haer-Wigman, Andy J. J. Beynon, Jaap Oostrik, Sjoert A. H. Pegge, Hannie Kremer, Cris P. P. Lanting, Ronald J. E. Pennings
Summary: The aim of this study is to describe the genotype and phenotype of a Dutch-German family with DFNA6/14/38-related hearing loss and suggest screenings for newborns in such families. A novel likely pathogenic WFS1 variant was found to co-segregate with the hearing loss in the family. The study also revealed indications of mild vestibular dysfunction in affected individuals.
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)