Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness

Bech-Hansen, N. Torben; Naylor, Margaret Jane; Maybaum, Tracy A.; Sparkes, Rebecca; Koop, Ben F.; Birch, David G.; Bergen, Arthur A. B.; Prinsen, Clemens; Polomeno, Robert C.; Gal, Andreas; Drack, Arlene V.; Musarella, Maria A.; Jacobson, Samuel G.; Young, Reginald H.F.; Weleber, Richard G.

doi:10.1038/81619

Cited by 293 publications

(211 citation statements)

References 27 publications

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“…CSNB-1 is due to mutation of the Nyx gene localized to Xp11.4 that encodes a novel protein, nyctalopin (Bech-Hansen et al, 2000;Bergen et al, 1996;Boycott et al, 1998;Rozzo et al, 1999). The Nob mouse also has a mutation in nyctalopin Pesch et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Shirato

Maeda

Miura

et al. 2008

Experimental Eye Research

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The purpose of this study was to determine the contributions of postreceptoral neurons to the lightadapted ERG of the Nob mouse, a model for complete-type congenital stationary night blindness (CSNB1) that lacks a b-wave from depolarizing bipolar cells. Ganzfeld ERGs were recorded from anesthetized adult control mice, control mice injected intravitreally with L-2-amino-4-phosphonobutyric acid (Control APB mice) to remove On pathway activity, and Nob mice. ERGs also were recorded after PDA (cis-2, 3-piperidine-dicarboxylic acid, 3-5 mM) was injected to block transmission to hyperpolarizing (Off) bipolar and horizontal cells, and all 3rd order neurons. Stimuli were brief (< 4 ms, 0.4 -2.5 log sc td s) and long (200 ms, 2.5 -4.6 log sc td) LED flashes (λmax = 513 nm, on a rod suppressing background (2.6 log sc td). Sinusoidal modulation of the LEDs (mean, 2.6 log sc td; contrast, 100%; 3 to 36 Hz) was used to study flicker ERGs.Brief-flash ERGs of Nob mice presented as long-lasting negative waves with a positive-going intrusion that started about 50 ms after the flash and peaked around 120 ms. Control APB mice had similar responses, and in both cases, PDA removed the positive-going intrusion. For long flashes, PDA removed a small, slow "d-wave" after light offset. With sinusoidal stimulation, the fundamental (F1) amplitude of control mice ERG peaked at 8 Hz (~70 μV). For Nob mice the peak was ~20 μV at 6 Hz before PDA and ~10 μV at 3 Hz or lower after PDA. F1 responses were present up to 21 Hz in control and Nob eyes and 15 Hz in Nob eyes after PDA. Between 3 and 6 Hz, F1 phase was 170°-210° more delayed in Nob than control mice; phase was hardly altered by PDA. With vector analysis, a substantial postreceptoral input to the Nob flicker ERG was revealed. In control mice, the second harmonic (F2) response showed peaks of ~10 μV at 3 Hz and 13 Hz. Nob mice showed almost no F2. In summary, in this study it was found that in Nob mice, postreceptoral neurons from the Off pathway make a positive-going contribution to the light-adapted flash ERG, and contribute substantially to sinusoidal flicker ERG.

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Section: Introductionmentioning

confidence: 99%

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Shirato

Maeda

Miura

et al. 2008

Experimental Eye Research

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“…Our 26 index patients included 16 males and 10 females. It is possible that some of the males have the X-linked form of complete stationary night blindness; however, they have not been evaluated for mutations in the NYX gene (25,26) that causes this form of night blindness. An X-linked inheritance pattern for many participating males could not be convincingly established through a family history.…”

Section: Dna Sequence Changes Found In Grm6mentioning

confidence: 99%

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6

Dryja

McGee²,

Berson³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

221

175

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We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20͞15 to 20͞40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform. bipolar cell ͉ glutamate receptor ͉ retina

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“…In contrast, cone function is more impaired in patients with the incomplete type, as can be seen in scotopic 30 Hertz flicker responses and dark adaptation tests. 3 -6 We and others have recently isolated the genes mutated in CSNB1 7,8 and CSNB2 families. 9,10 The CACNA1F gene, mutated in CSNB2 families, comprises 48 exons and codes for a protein which consists of 1966 amino acids showing high homology to a1-subunits of L-type calcium channels.…”

Section: Introductionmentioning

confidence: 99%

Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina

Wutz¹,

Sauer

Zrenner³

et al. 2002

Eur J Hum Genet

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X-linked CSNB patients may exhibit myopia, nystagmus, strabismus and ERG abnormalities of the Schubert-Bornschein type. We recently identified the retina-specific L-type calcium channel a1 subunit gene CACNA1F localised to the Xp11.23 region, which is mutated in families showing the incomplete type (CSNB2). Here, we report comprehensive mutation analyses in the 48 CACNA1F exons in 36 families, most of them from Germany. All families were initially diagnosed as having the incomplete type of CSNB, except for two which have been designated as Å land Island eye disease (Å IED)-like. Out of 33 families, a total of 30 different mutations were identified, of which 24 appear to be unique for the German population. The mutations, 20 of which are published here for the first time, were found to be equally distributed over the entire gene sequence. No mutation could be found in a classic Å IED family previously shown to map to the CSNB2 interval. Cacna1f expression in photoreceptor-negative mice strains indicate that the gene is expressed in the outer nuclear, the inner nuclear, and the ganglion cell layer. Such a distribution points to the central role of calcium regulation in the interaction of retinal cells that mediate signal transmission.

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Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness

Cited by 293 publications

References 27 publications

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6

Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina

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