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Arlene V Drack - One of the best experts on this subject based on the ideXlab platform.
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Presentation of TRPM1-Associated Congenital Stationary Night Blindness in Children.
JAMA ophthalmology, 2018Co-Authors: Virginia Miraldi Utz, Wanda Pfeifer, Susannah Q. Longmuir, Richard J. Olson, Kai Wang, Arlene V DrackAbstract:Importance Congenital stationary night blindness (CSNB) implies a stable condition, with the major symptom being Nyctalopia present at birth. Pediatric clinical presentation and the course of different genetic subtypes of CSNB have not, to our knowledge, been well described in the era of molecular genetic diagnosis. Objective To describe the presentation and longitudinal clinical characteristics of pediatric patients with molecularly confirmed TRPM1 -associated complete CSNB (cCSNB). Design, Setting, Participants This study was conducted at the University of Iowa from January 1, 1990, to July 1, 2015, and was a retrospective, longitudinal case series of 7 children (5 [71.4%] female) with TRPM1 -associated cCSNB followed up for a mean (SD) of 11.1 (2.8) years. Main Outcomes and Measures History, ophthalmologic examination findings, full-field electroretinogram (ffERG) results, full-field stimulus threshold testing results, Goldmann visual field results, optical coherence tomography results, and molecular genetic results were evaluated. Presenting symptoms and signs, the correlation of refractive error with electroretinography, and clinical evolution were analyzed. Results Seven patients (5 [71.4%] female) presented early in childhood with strabismus (n = 6 [86%]), myopia (n = 5 [71%]), and/or nystagmus (n = 3 [43%]). The mean (SD) age at presentation was 8 (4) months and for receiving a diagnosis by ffERG was 7.3 years, with molecular diagnosis at 9.7 years. The mean (SD) length of follow-up was 11 (2.8) years. The best-corrected visual acuity at the most recent visit averaged 20/30 in the better-seeing eye (range, 20/20-20/60). The mean (SD) initial refraction was −2.80 (4.42) diopters (D) and the mean refraction at the most recent visit was −8.75 (3.53) D (range, −4.00 to −13.75 D), with the greatest rate of myopic shift before age 5 years. Full-field electroretinogram results were electronegative, consistent with cCSNB, without a significant change in amplitude over time. No patient or parent noted night blindness at presentation; however, subjective Nyctalopia was eventually reported in 5 of 7 patients (71%). The full-field stimulus threshold testing results were moderately subnormal (−29.7 [3.8] dB; normal −59.8 [4.0] dB). Goldmann visual field results were significant for full I-4e, but constricted I-2e isopter. Eight different mutations or rare variants in TRPM1 predicted to be pathogenic were detected, with 3 novel variants. Conclusions and Relevance Children with TRPM1 -associated cCSNB presented before school age with progressive myopia as well as strabismus and nystagmus (but not Nyctalopia), with stable, electronegative ffERG results, mildly subnormal full-field stimulus threshold testing results, and a constricted I2e isopter on perimetry. These findings suggest that ffERG and cCSNB genetic testing should be considered for children who present with early-onset myopia, especially in the presence of strabismus and/or nystagmus, and that TRPM1 -associated cCSNB is a channelopathy that may present without complaints of night blindness in childhood.
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mutations in nyx encoding the leucine rich proteoglycan nyctalopin cause x linked complete congenital stationary night blindness
Nature Genetics, 2000Co-Authors: Torben N Bechhansen, Margaret J Naylor, Tracy A Maybaum, Rebecca Sparkes, Ben F Koop, David G Birch, Arthur A B Bergen, Clemens F M Prinsen, Robert Polomeno, Arlene V DrackAbstract:Mutations in NYX , encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness
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Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness
Nature Genetics, 2000Co-Authors: N.torben Bech-hansen, Margaret J Naylor, Tracy A Maybaum, David G Birch, Arthur A B Bergen, Clemens F M Prinsen, Robert Polomeno, Rebecca L. Sparkes, Ben Koop, Arlene V DrackAbstract:During development, visual photoreceptors, bipolar cells and other neurons establish connections within the retina enabling the eye to process visual images over approximately 7 log units of illumination^ 1 . Within the retina, cells that respond to light increment and light decrement are separated into ON- and OFF-pathways. Hereditary diseases are known to disturb these retinal pathways, causing either progressive degeneration or stationary deficits^ 2 . Congenital stationary night blindness (CSNB) is a group of stable retinal disorders that are characterized by abnormal night vision. Genetic subtypes of CSNB have been defined and different disease actions have been postulated^ 3 , 4 , 5 . The molecular bases have been elucidated in several subtypes, providing a better understanding of the disease mechanisms and developmental retinal neurobiology^ 2 . Here we have studied 22 families with 'complete' X-linked CSNB (CSNB1; MIM 310500; ref. 4 ) in which affected males have night blindness, some photopic vision loss and a defect of the ON-pathway. We have found 14 different mutations, including 1 founder mutation in 7 families from the United States, in a novel candidate gene, NYX . NYX , which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the small leucine-rich proteoglycan (SLRP) family^ 6 . The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB.
Maureen A Mccall - One of the best experts on this subject based on the ideXlab platform.
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nyctalopin expression in retinal bipolar cells restores visual function in a mouse model of complete x linked congenital stationary night blindness
Journal of Neurophysiology, 2007Co-Authors: Ronald G Gregg, Neal S Peachey, Maarten Kamermans, Jan Klooster, Peter D Lukasiewicz, Kirstan A Vessey, Maureen A MccallAbstract:Mutations in the NYX gene that encodes the protein nyctalopin cause congenital stationary night blindness type 1. In no b-wave (nob) mice, a mutation in Nyx results in a functional phenotype that includes the absence of the electroretinogram b-wave and abnormal spontaneous and light-evoked activity in retinal ganglion cells (RGCs). In contrast, there is no morphological abnormality in the retina at either the light or electron microscopic levels. These functional deficits suggest that nyctalopin is required for normal synaptic transmission between retinal photoreceptors and depolarizing bipolar cells (DBCs). However, the synaptic etiology and, specifically, the exact location and function of nyctalopin, remain uncertain. We show that nob DBCs fail to respond to exogenous application of the photoreceptor neurotransmitter, glutamate, thus demonstrating a postsynaptic deficit in photoreceptor to bipolar cell communication. To determine if postsynaptic expression of nyctalopin is necessary and sufficient to rescue the nob phenotype, we constructed transgenic mice that expressed an EYFP-nyctalopin fusion protein on the dendritic tips of the DBCs. Immunohistochemical and ultrastructural studies verified that fusion protein expression was limited to the DBC dendritic tips. Fusion gene expression in nob mice restored normal outer and inner visual function as determined by the electroretinogram and RGC spontaneous and evoked responses. Together, our data show that nyctalopin expression on DBC dendrites is required for normal function of the murine retina.
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nyctalopin expression in retinal bipolar cells restores visual function in a mouse model of complete x linked congenital stationary night blindness
Journal of Neurophysiology, 2007Co-Authors: Ronald G Gregg, Neal S Peachey, Maarten Kamermans, Jan Klooster, Peter D Lukasiewicz, Kirstan A Vessey, Maureen A MccallAbstract:Mutations in the NYX gene that encodes the protein nyctalopin cause congenital stationary night blindness type 1. In no b-wave (nob) mice, a mutation in Nyx results in a functional phenotype that i...
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immunohistochemical analysis of the outer plexiform layer in the nob mouse shows no abnormalities
Visual Neuroscience, 2003Co-Authors: Sherry L Ball, Ronald G Gregg, Maureen A Mccall, Machelle T. Pardue, Neal S PeacheyAbstract:In the nob mouse, a mutation in nyctalopin results in a loss of signal transmission from photoreceptors to depolarizing bipolar cells (DBCs). We used immunohistochemical techniques to assess the expression pattern of proteins found at either the photoreceptor terminal or bipolar cell dendrites within the outer plexiform layer. We labeled normal and nob retinas with antibodies against mGluR6, PKC, G0a, bassoon, PSD-95, the a1F subunit of voltage-gated calcium channels, trkB, and dystrophin. All labeling patterns in nob and normal retinas were comparable to those previously reported in mouse retina. Our results indicate that the absence of nyctalopin does not disrupt the expression pattern of other proteins known to be required for synaptic transmission.
Ronald G Gregg - One of the best experts on this subject based on the ideXlab platform.
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A Role for Nyctalopin, a Small Leucine-Rich Repeat Protein, in Localizing the TRP Melastatin 1 Channel to Retinal Depolarizing Bipolar Cell Dendrites
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011Co-Authors: Jillian N. Pearring, Chieko Koike, Pasano Bojang, Yin Shen, Takahisa Furukawa, Scott Nawy, Ronald G GreggAbstract:Expression of channels to specific neuronal sites can critically impact their function and regulation. Currently, the molecular mechanisms underlying this targeting and intracellular trafficking of transient receptor potential (TRP) channels remain poorly understood, and identifying proteins involved in these processes will provide insight into underlying mechanisms. Vision is dependent on the normal function of retinal depolarizing bipolar cells (DBCs), which couple a metabotropic glutamate receptor 6 to the TRP melastatin 1 (TRPM1) channel to transmit signals from photoreceptors. We report that the extracellular membrane-attached protein nyctalopin is required for the normal expression of TRPM1 on the dendrites of DBCs in mus musculus. Biochemical and genetic data indicate that nyctalopin and TRPM1 interact directly, suggesting that nyctalopin is acting as an accessory TRP channel subunit critical for proper channel localization to the synapse.
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nyctalopin expression in retinal bipolar cells restores visual function in a mouse model of complete x linked congenital stationary night blindness
Journal of Neurophysiology, 2007Co-Authors: Ronald G Gregg, Neal S Peachey, Maarten Kamermans, Jan Klooster, Peter D Lukasiewicz, Kirstan A Vessey, Maureen A MccallAbstract:Mutations in the NYX gene that encodes the protein nyctalopin cause congenital stationary night blindness type 1. In no b-wave (nob) mice, a mutation in Nyx results in a functional phenotype that includes the absence of the electroretinogram b-wave and abnormal spontaneous and light-evoked activity in retinal ganglion cells (RGCs). In contrast, there is no morphological abnormality in the retina at either the light or electron microscopic levels. These functional deficits suggest that nyctalopin is required for normal synaptic transmission between retinal photoreceptors and depolarizing bipolar cells (DBCs). However, the synaptic etiology and, specifically, the exact location and function of nyctalopin, remain uncertain. We show that nob DBCs fail to respond to exogenous application of the photoreceptor neurotransmitter, glutamate, thus demonstrating a postsynaptic deficit in photoreceptor to bipolar cell communication. To determine if postsynaptic expression of nyctalopin is necessary and sufficient to rescue the nob phenotype, we constructed transgenic mice that expressed an EYFP-nyctalopin fusion protein on the dendritic tips of the DBCs. Immunohistochemical and ultrastructural studies verified that fusion protein expression was limited to the DBC dendritic tips. Fusion gene expression in nob mice restored normal outer and inner visual function as determined by the electroretinogram and RGC spontaneous and evoked responses. Together, our data show that nyctalopin expression on DBC dendrites is required for normal function of the murine retina.
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nyctalopin expression in retinal bipolar cells restores visual function in a mouse model of complete x linked congenital stationary night blindness
Journal of Neurophysiology, 2007Co-Authors: Ronald G Gregg, Neal S Peachey, Maarten Kamermans, Jan Klooster, Peter D Lukasiewicz, Kirstan A Vessey, Maureen A MccallAbstract:Mutations in the NYX gene that encodes the protein nyctalopin cause congenital stationary night blindness type 1. In no b-wave (nob) mice, a mutation in Nyx results in a functional phenotype that i...
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immunohistochemical analysis of the outer plexiform layer in the nob mouse shows no abnormalities
Visual Neuroscience, 2003Co-Authors: Sherry L Ball, Ronald G Gregg, Maureen A Mccall, Machelle T. Pardue, Neal S PeacheyAbstract:In the nob mouse, a mutation in nyctalopin results in a loss of signal transmission from photoreceptors to depolarizing bipolar cells (DBCs). We used immunohistochemical techniques to assess the expression pattern of proteins found at either the photoreceptor terminal or bipolar cell dendrites within the outer plexiform layer. We labeled normal and nob retinas with antibodies against mGluR6, PKC, G0a, bassoon, PSD-95, the a1F subunit of voltage-gated calcium channels, trkB, and dystrophin. All labeling patterns in nob and normal retinas were comparable to those previously reported in mouse retina. Our results indicate that the absence of nyctalopin does not disrupt the expression pattern of other proteins known to be required for synaptic transmission.
Robert Polomeno - One of the best experts on this subject based on the ideXlab platform.
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mutations in nyx encoding the leucine rich proteoglycan nyctalopin cause x linked complete congenital stationary night blindness
Nature Genetics, 2000Co-Authors: Torben N Bechhansen, Margaret J Naylor, Tracy A Maybaum, Rebecca Sparkes, Ben F Koop, David G Birch, Arthur A B Bergen, Clemens F M Prinsen, Robert Polomeno, Arlene V DrackAbstract:Mutations in NYX , encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness
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Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness
Nature Genetics, 2000Co-Authors: N.torben Bech-hansen, Margaret J Naylor, Tracy A Maybaum, David G Birch, Arthur A B Bergen, Clemens F M Prinsen, Robert Polomeno, Rebecca L. Sparkes, Ben Koop, Arlene V DrackAbstract:During development, visual photoreceptors, bipolar cells and other neurons establish connections within the retina enabling the eye to process visual images over approximately 7 log units of illumination^ 1 . Within the retina, cells that respond to light increment and light decrement are separated into ON- and OFF-pathways. Hereditary diseases are known to disturb these retinal pathways, causing either progressive degeneration or stationary deficits^ 2 . Congenital stationary night blindness (CSNB) is a group of stable retinal disorders that are characterized by abnormal night vision. Genetic subtypes of CSNB have been defined and different disease actions have been postulated^ 3 , 4 , 5 . The molecular bases have been elucidated in several subtypes, providing a better understanding of the disease mechanisms and developmental retinal neurobiology^ 2 . Here we have studied 22 families with 'complete' X-linked CSNB (CSNB1; MIM 310500; ref. 4 ) in which affected males have night blindness, some photopic vision loss and a defect of the ON-pathway. We have found 14 different mutations, including 1 founder mutation in 7 families from the United States, in a novel candidate gene, NYX . NYX , which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the small leucine-rich proteoglycan (SLRP) family^ 6 . The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB.
Clemens F M Prinsen - One of the best experts on this subject based on the ideXlab platform.
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mutations in nyx encoding the leucine rich proteoglycan nyctalopin cause x linked complete congenital stationary night blindness
Nature Genetics, 2000Co-Authors: Torben N Bechhansen, Margaret J Naylor, Tracy A Maybaum, Rebecca Sparkes, Ben F Koop, David G Birch, Arthur A B Bergen, Clemens F M Prinsen, Robert Polomeno, Arlene V DrackAbstract:Mutations in NYX , encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness
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Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness
Nature Genetics, 2000Co-Authors: N.torben Bech-hansen, Margaret J Naylor, Tracy A Maybaum, David G Birch, Arthur A B Bergen, Clemens F M Prinsen, Robert Polomeno, Rebecca L. Sparkes, Ben Koop, Arlene V DrackAbstract:During development, visual photoreceptors, bipolar cells and other neurons establish connections within the retina enabling the eye to process visual images over approximately 7 log units of illumination^ 1 . Within the retina, cells that respond to light increment and light decrement are separated into ON- and OFF-pathways. Hereditary diseases are known to disturb these retinal pathways, causing either progressive degeneration or stationary deficits^ 2 . Congenital stationary night blindness (CSNB) is a group of stable retinal disorders that are characterized by abnormal night vision. Genetic subtypes of CSNB have been defined and different disease actions have been postulated^ 3 , 4 , 5 . The molecular bases have been elucidated in several subtypes, providing a better understanding of the disease mechanisms and developmental retinal neurobiology^ 2 . Here we have studied 22 families with 'complete' X-linked CSNB (CSNB1; MIM 310500; ref. 4 ) in which affected males have night blindness, some photopic vision loss and a defect of the ON-pathway. We have found 14 different mutations, including 1 founder mutation in 7 families from the United States, in a novel candidate gene, NYX . NYX , which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the small leucine-rich proteoglycan (SLRP) family^ 6 . The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB.