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Ryoikibetsu Shokogun Shirizu 2000
Review
Topics: Diagnosis, Differential; Eye Diseases, Hereditary; Eye Proteins; Genes, Recessive; Humans; Mutation; Nerve Tissue Proteins; Nervous System Diseases; Prognosis; X Chromosome
PubMed: 11032012
DOI: No ID Found -
Proceedings of the National Academy of... Sep 2021Mutations in the gene for Norrie disease protein () cause syndromic deafness and blindness. We show here that cochlear function in an knockout mouse deteriorated with...
Mutations in the gene for Norrie disease protein () cause syndromic deafness and blindness. We show here that cochlear function in an knockout mouse deteriorated with age: At P3-P4, hair cells (HCs) showed progressive loss of Pou4f3 and Gfi1, key transcription factors for HC maturation, and Myo7a, a specialized myosin required for normal function of HC stereocilia. Loss of expression of these genes correlated to increasing HC loss and profound hearing loss by 2 mo. We show that overexpression of the gene in neonatal supporting cells or, remarkably, up-regulation of canonical Wnt signaling in HCs rescued HCs and cochlear function. We conclude that Ndp secreted from supporting cells orchestrates a transcriptional network for the maintenance and survival of HCs and that increasing the level of β-catenin, the intracellular effector of Wnt signaling, is sufficient to replace the functional requirement for in the cochlea.
Topics: Animals; Animals, Newborn; DNA-Binding Proteins; Eye Proteins; Female; Hair Cells, Auditory; Hearing Loss; Homeodomain Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins; Transcription Factor Brn-3C; Transcription Factors; Wnt Signaling Pathway
PubMed: 34544869
DOI: 10.1073/pnas.2106369118 -
Progress in Retinal and Eye Research May 2021X-linked retinopathies represent a significant proportion of monogenic retinal disease. They include progressive and stationary conditions, with and without syndromic... (Review)
Review
X-linked retinopathies represent a significant proportion of monogenic retinal disease. They include progressive and stationary conditions, with and without syndromic features. Many are X-linked recessive, but several exhibit a phenotype in female carriers, which can help establish diagnosis and yield insights into disease mechanisms. The presence of affected carriers can misleadingly suggest autosomal dominant inheritance. Some disorders (such as RPGR-associated retinopathy) show diverse phenotypes from variants in the same gene and also highlight limitations of current genetic sequencing methods. X-linked disease frequently arises from loss of function, implying potential for benefit from gene replacement strategies. We review X-inactivation and X-linked inheritance, and explore burden of disease attributable to X-linked genes in our clinically and genetically characterised retinal disease cohort, finding correlation between gene transcript length and numbers of families. We list relevant genes and discuss key clinical features, disease mechanisms, carrier phenotypes and novel experimental therapies. We consider in detail the following: RPGR (associated with retinitis pigmentosa, cone and cone-rod dystrophy), RP2 (retinitis pigmentosa), CHM (choroideremia), RS1 (X-linked retinoschisis), NYX (complete congenital stationary night blindness (CSNB)), CACNA1F (incomplete CSNB), OPN1LW/OPN1MW (blue cone monochromacy, Bornholm eye disease, cone dystrophy), GPR143 (ocular albinism), COL4A5 (Alport syndrome), and NDP (Norrie disease and X-linked familial exudative vitreoretinopathy (FEVR)). We use a recently published transcriptome analysis to explore expression by cell-type and discuss insights from electrophysiology. In the final section, we present an algorithm for genes to consider in diagnosing males with non-syndromic X-linked retinopathy, summarise current experimental therapeutic approaches, and consider questions for future research.
Topics: Calcium Channels, L-Type; Eye Proteins; Female; Genes, X-Linked; Genetic Diseases, X-Linked; Humans; Male; Mutation; Night Blindness; Phenotype; Retinal Degeneration
PubMed: 32860923
DOI: 10.1016/j.preteyeres.2020.100898 -
Methods in Molecular Biology (Clifton,... 2009Single nucleotide polymorphism (SNP) is the simplest form of DNA variation among individuals. These simple changes can be of transition or transversion type and they... (Review)
Review
Single nucleotide polymorphism (SNP) is the simplest form of DNA variation among individuals. These simple changes can be of transition or transversion type and they occur throughout the genome at a frequency of about one in 1,000 bp. They may be responsible for the diversity among individuals, genome evolution, the most common familial traits such as curly hair, interindividual differences in drug response, and complex and common diseases such as diabetes, obesity, hypertension, and psychiatric disorders. SNPs may change the encoded amino acids (nonsynonymous) or can be silent (synonymous) or simply occur in the noncoding regions. They may influence promoter activity (gene expression), messenger RNA (mRNA) conformation (stability), and subcellular localization of mRNAs and/or proteins and hence may produce disease. Therefore, identification of numerous variations in genes and analysis of their effects may lead to a better understanding of their impact on gene function and health of an individual. This improved knowledge may provide a starting point for the development of new, useful SNP markers for medical testing and a safer individualized medication to treat the most common devastating disorders. This will revolutionize the medical field in the future. To illustrate the effect of SNPs on gene function and phenotype, this minireview focuses on evidences revealing the impact of SNPs on the development and progression of three human eye disorders (Norrie disease, familial exudative vitreoretinopathy, and retinopathy of prematurity) that have overlapping clinical manifestations.
Topics: Animals; Genes; Humans; Infant, Newborn; Nervous System Diseases; Phenotype; Polymorphism, Single Nucleotide; Retinopathy of Prematurity; Wnt Proteins
PubMed: 19768584
DOI: 10.1007/978-1-60327-411-1_1 -
BMC Research Notes May 2021Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no...
OBJECTIVE
Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein-protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship.
RESULT
Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.
Topics: Animals; Blindness; Eye Proteins; Genetic Diseases, X-Linked; Humans; Mice; Mutation; Nervous System Diseases; Retina; Retinal Degeneration; Retinoschisis; Spasms, Infantile
PubMed: 34039417
DOI: 10.1186/s13104-021-05617-5 -
Cells Nov 2023Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct... (Review)
Review
Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function, and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway, such as and have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as and some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (, ) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene () suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goal of this review is to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.
Topics: Humans; Child; Familial Exudative Vitreoretinopathies; Endothelial Cells; Tetraspanins; Retinal Diseases; Vascular Diseases; Frizzled Receptors; DNA-Binding Proteins; Transcription Factors
PubMed: 37947657
DOI: 10.3390/cells12212579 -
Human Molecular Genetics 1995The Norrie disease and MAO genes are tandemly arranged in the p11.4-p11.3 region of the human X chromosome in the order tel-MAOA-MAOB-NDP-cent. This relationship is... (Review)
Review
The Norrie disease and MAO genes are tandemly arranged in the p11.4-p11.3 region of the human X chromosome in the order tel-MAOA-MAOB-NDP-cent. This relationship is conserved in the mouse in the order tel-MAOB-MAOA-NDP-cent. The MAO genes appear to have arisen by tandem duplication of an ancestral MAO gene, but their positional relationship to NDP appears to be random. Distinctive X-linked syndromes have been described for mutations in the MAOA and NDP genes, and in addition, individuals have been identified with contiguous gene syndromes due to chromosomal deletions which encompass two or three of these genes. Loss of function of the NDP gene causes a syndrome of congenital blindness and progressive hearing loss, sometimes accompanied by signs of CNS dysfunction, including variable mental retardation and psychiatric symptoms. Other mutations in the NDP gene have been found to underlie another X-linked eye disease, exudative vitreo-retinopathy. An MAOA deficiency state has been described in one family to date, with features of altered amine and amine metabolite levels, low normal intelligence, apparent difficulty in impulse control and cardiovascular difficulty in affected males. A contiguous gene syndrome in which all three genes are lacking, as well as other as yet unidentified flanking genes, results in severe mental retardation, small stature, seizures and congenital blindness, as well as altered amine and amine metabolites. Issues that remain to be resolved are the function of the NDP gene product, the frequency and phenotype of the MAOA deficiency state, and the possible occurrence and phenotype of an MAOB deficiency state.
Topics: Animals; Blindness; Chromosome Mapping; Genetic Linkage; Humans; Monoamine Oxidase; Syndrome; X Chromosome
PubMed: 8541872
DOI: 10.1093/hmg/4.suppl_1.1729 -
Cell and Tissue Research May 2023Endothelial cells play a major part in the regulation of vascular permeability and angiogenesis. According to their duty to fit the needs of the underlying tissue,... (Review)
Review
Endothelial cells play a major part in the regulation of vascular permeability and angiogenesis. According to their duty to fit the needs of the underlying tissue, endothelial cells developed different subtypes with specific endothelial microdomains as caveolae, fenestrae and transendothelial channels which regulate nutrient exchange, leukocyte migration, and permeability. These microdomains can exhibit diaphragms that are formed by the endothelial cell-specific protein plasmalemma vesicle-associated protein (PLVAP), the only known protein component of these diaphragms. Several studies displayed an involvement of PLVAP in diseases as cancer, traumatic spinal cord injury, acute ischemic brain disease, transplant glomerulopathy, Norrie disease and diabetic retinopathy. Besides an upregulation of PLVAP expression within these diseases, pro-angiogenic or pro-inflammatory responses were observed. On the other hand, loss of PLVAP in knockout mice leads to premature mortality due to disrupted homeostasis. Generally, PLVAP is considered as a major factor influencing the permeability of endothelial cells and, finally, to be involved in the regulation of vascular permeability. Following these observations, PLVAP is debated as a novel therapeutic target with respect to the different vascular beds and tissues. In this review, we highlight the structure and functions of PLVAP in different endothelial types in health and disease.
Topics: Animals; Brain; Capillary Permeability; Carrier Proteins; Diabetic Retinopathy; Endothelial Cells; Membrane Proteins; Humans
PubMed: 36781482
DOI: 10.1007/s00441-023-03741-1 -
Journal Francais D'ophtalmologie May 2020
Topics: Blindness; Cameroon; Child; Corneal Opacity; Eye Proteins; Genetic Diseases, X-Linked; Humans; Magnetic Resonance Imaging; Male; Mutation, Missense; Nerve Tissue Proteins; Nervous System Diseases; Nystagmus, Pathologic; Retinal Degeneration; Retinal Dystrophies; Spasms, Infantile; Ultrasonography
PubMed: 32381368
DOI: 10.1016/j.jfo.2019.09.023