Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A common cause of pathological nystagmus is malfunction of the mechanism by which the brain integrates eye velocity signals to produce eye position commands. For horizontal gaze, neurons in the nucleus prepositus hypoglossi-medial vestibular nucleus region (NPH-MVN) play a vital role in this neural integrator function. We studied the effects on gaze stability of pharmacological intervention in the NPH-MVN of monkeys by microinjections of eight drugs. Agents with agonist or antagonist actions at gamma-aminobutyric acid (GABA), glutamate, and kainate receptors all caused gaze-evoked nystagmus with centripetal eye drifts; glycine and strychnine had no effect. When the GABAA-agonist muscimol was injected near the center of MVN, the eyes drifted away from the central position with increasing-velocity waveforms, implying an unstable neural integrator. The observed effects of these drugs on gaze stability may be related to inactivation either of neurons within NPH-MVN or the cerebellar projections to them that control the fidelity of neural integration. Drugs that influence GABA or glutamine transmission may have a role in the treatment of nystagmus due to an abnormal neural integrator.
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PMID:Nystagmus induced by pharmacological inactivation of the brainstem ocular motor integrator in monkey. 1075 64

A 47-year-old Japanese woman undergoing maintenance hemodialysis (HD) was admitted to our hospital because of poisoning with the herbicide bialaphos. Respiratory arrest and loss of consciousness ensued rapidly, accompanied by convulsions and nystagmus. Treatment with HD and direct hemoperfusion, followed by HD alone, effectively removed bialaphos and its chief toxic metabolite (L-AMPB) from the circulation (bialaphos decreased from 0.33 to < 0.05 microg/ml and L-AMPB from 14 to 0.86 microg/ml). The glutamate concentration improved gradually after the removal of bialaphos and L-AMPB from plasma (plasma glutamate concentration: 250.4 nmol/l on day 5 to 120.6 nmol/l on day 26). Decreased glutamine concentration in cerebrospinal fluid was demonstrated for the first time as well as in plasma, indicating glutamine synthetase inhibition not only in plants but also in humans by bialaphos poisoning.
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PMID:Decreased plasma and cerebrospinal fluid glutamine concentrations in a patient with bialaphos poisoning. 1172 95

Idiopathic congenital nystagmus (ICN) is a genetically heterogeneous eye movement disorder which seriously reduces childhood visual acuity. X-linked inheritance is the most common pattern, and mutations in FERM domain-containing protein 7 (FRMD7) are the major cause. Here, we recruited a four-generation Chinese family with X-linked ICN for the causative mutational screening of FRMD7. A novel missense variant, c.805 A > C, was identified in the proband. The mutation was confirmed in all the affected individuals but was not detected in unaffected family members or 100 unrelated Chinese male controls. The mutation causes a substitution of lysine to glutamine at position 269 (p.Lys269Gln, K269Q). The FRMD7 mutant inhibits the formation and extension of neurites. Moreover, the mutation disrupts FRMD7 interaction with calcium/calmodulin-dependent serine protein kinase and neurite formation. Together, our data expand the mutation spectrum of FRMD7 causing ICN and provide an insight into the pathogenesis of nystagmus.
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PMID:Identification and functional characterization of a novel missense mutation in FRMD7 responsible for idiopathic congenital nystagmus. 3057

Foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis is an autosomal recessive disorder arising from SLC38A8 mutations. SLC38A8 is a putative glutamine transporter with strong expression within the photoreceptor layer in the retina. Previous studies have been limited due to lack of quantitative data on retinal development and nystagmus characteristics. In this multi-centre study, a custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report 16 novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. Ninety percent of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterized the retinal development in vivo in patients with SLC38A8 mutations using high-resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. Loss of foveal specialization features such as outer segment lengthening implies reduced foveal cone density, which contributes to reduced visual acuity. Unlike other disorders (such as albinism or PAX6 mutations) which exhibit a spectrum of foveal hypoplasia, SLC38A8 mutations have arrest of retinal development at an earlier stage resulting in a more under-developed retina and severe phenotype.
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PMID:SLC38A8 mutations result in arrested retinal development with loss of cone photoreceptor specialization. 3274 12