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)

Adult goldfish had one tectal lobe removed surgically, and several months later, the eye contralateral to the missing tectum was injected with radioactive proline. Radioautographs of the brains were studied to trace the paths and termination sites of the optic fibers. The optic tract decussated at the chiasm, as normally, but then ran caudally in a large neuroma on the tectum-less side of the brain. Substantial numbers of fibers left this neuroma to enter two or more of five commissures, through which they recrossed the midline. These commissures: transverse, minor, horizontal, posterior and ansate, ordinarily contain few or no optic fibers. All are normally linked with the tectum. Negligible numbers of aberrant optic fibers recrossed the midline elsewhere. On the intact side of the brain, ipsilateral to the injected eye, the optic fibers innervated some or all of the nuclei and areas normally served by contralateral retinal fibers. An earlier behavioral study of these same fish had shown that some of them made reversed optokinetic nystagmus in response to stripe movement seen by the eye projecting ipsilaterally; others failed to respond to stimuli through this eye. In all the reversed responders, a caudal group of retinal projection sites was labeled ipsilaterally. This included the basal optic nucleus and the caudal portions of nucleus dorsolateralis thalami and area pretectalis. In the non-responders, these targets were not labeled ipsilaterally. Together, these results suggest that one or more of these three sites is or are responsible for optokinetic nystagmus in normal goldfish.
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PMID:The paths and destinations of the induced ipsilateral retinal projection in goldfish. 67 Aug 59

Retinal projections to the pretectal and terminal accessory optic nuclei were studied in normal wild-type mice and mutant mice with abnormal optokinetic nystagmus (OKN, Mangini, Vanable, Williams, and Pinto: J. Comp. Neurol. 241:191-209, '85). The mutants used were pearl, which exhibits an inverted OKN in response to stimulation of only the temporal retina, and beige and beige-J, which show inverted OKN in response to stimulation of only the temporal retina and, in addition, exhibit eye movements with a vertical component in response to horizontally moving, full-field stimuli. These projections were studied following intraocular injections of 3H-proline or horseradish peroxidase (HRP) with, respectively, light microscopic autoradiography or HRP histochemistry. In wild-type mice, strong contralateral retinal projections covered the entire nucleus of the optic tract, the anterior and posterior divisions of the olivary pretectal nucleus, and the posterior pretectal nucleus. Similar heavy contralateral projections were distributed over the dorsal and medial terminal nuclei of the accessory optic system. Also, terminals sparsely covered the entire neuropil of the contralateral lateral terminal nucleus in some but not all wild-type mice. The most prominent accessory optic input was to the medial terminal nucleus and was provided by the inferior fasciculus of the accessory optic tract. A typical mammalian superior fasciculus of the accessory optic system with anterior, middle, and posterior components was present. Ipsilateral label was found in anterior and posterior olivary pretectal nuclei in all of the wild-type animals, but was found inconsistently in the ipsilateral terminal accessory optic nuclei. The pattern of contralateral retinal projection to the nucleus of the optic tract and posterior pretectal nucleus in mutants was indistinguishable from that seen in the normal wild-type mice. However, retinal inputs to the ipsilateral anterior and posterior olivary pretectal nuclei were significantly reduced in pearl mutants and were exceedingly sparse in the beige and beige-J mutant mice, while the contralateral inputs to these nuclei were increased in a complementary fashion in the mutants. The labeling of the accessory optic input to the contralateral dorsal terminal nucleus appeared to be substantially reduced in all of the mutant mice. The size of the principal accessory optic fascicle, the inferior fasciculus, was significantly smaller in beige, beige-J, and pearl mice; this reduction was greater in the beige and beige-J than in the pearl mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Retinopretectal and accessory optic projections of normal mice and the OKN-defective mutant mice beige, beige-J, and pearl. 358 47

A non-neoplastic syndrome of inappropriate secretion of TSH (ITSHS) was diagnosed in a hemithyroidectomized and clinically euthyroid 44-yr-old man, who also exhibited limping (Perthes' disease), genu valgum, pes supinatus and lateral nystagmus. Computed tomography demonstrated an enlarged sella turcica due to empty sella. Baseline serum T3, T4, free T3, free T4 and TSH fluctuated between 179 and 274 ng/dl, 6.0 and 13.2 micrograms/dl, 4.2 and 6.0 pg/ml, 7.6 and 15.3 pg/ml, and 4.3 and 33.0 microU/ml, respectively. Serum alpha-TSH subunit was repeatedly normal (0.36-0.69 ng/ml) over the follow-up period (greater than 3 yr). No changes in serum liver enzymes and lipids were observed after thyroid hormone administration, whereas red blood cell glucose-6-phosphate dehydrogenase (G-6-PD) and urinary OH-proline were slightly enhanced during 120 micrograms/day L-T3 regimen. This also resulted in an inappropriately normal glucagon-stimulated cAMP levels. Tachycardia was experienced only during L-T3 and very high L-T4 dose treatments. Therefore, the patient showed some evidence for thyroid hormone peripheral refractoriness. Patient's TSH was physiologically responsive to agents (thyrotropin releasing hormone, methimazole, the dopamine antagonists domperidone and sulpiride) known to elicit its release into circulation, while it responded paradoxically to those which normally inhibit TSH secretion. In fact, the infusion of somatostatin (320 micrograms/h) or dopamine (4 micrograms/Kg/min), and the oral administration of bromocriptine or nomifensine (two dopamine agonists) or corticosteroids (dexamethasone) provoked an unexpected elevation of both unstimulated and TRH-stimulated TSH levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal daily periodicity of serum thyrotropin (TSH) and evidence for defective TSH suppression in a case of non-neoplastic syndrome of inappropriate TSH secretion. 358 59

The ipsilateral and contralateral retinal projection was studied in pigmented rabbits and in 3 strains of albino rabbits by anterograde transport of [3H]proline and [3H]fucose combined with autoradiographic techniques. Special attention was paid to the terminals in the pretectal area of both the pigmented and albino strains. On the contralateral side terminal labeling was found in both pigmented and albino rabbits in the nucleus of the optic tract (NOT), the anterior pretectal nucleus (PA), the posterior pretectal nucleus (PP) and the pretectal olivary nucleus (PO). Ipsilaterally labeling was found only in the pigmented strain in small patches in the PP. Ipsilateral projection was not found in the albinos in the pretectal area. The results are in agreement with the findings of Scalia in pigmented rabbits. The absence of ipsilateral labeling in the pretectal region in albinos is in contrast with earlier findings of Giolli and Takahashi et al., in pigmented rabbits but is in agreement with the observations of Takahashi and Oyster. Since no radioactively labeled fibers were found to project to the NOT in either pigmented or albino rabbits, these results do not support the hypothesis of Collewijn that the inverted optokinetic nystagmus in albinos is due to misrouting of the ipsilateral retinal fibers to the NOT.
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PMID:Retinopretectal projections in albino and pigmented rabbits: an autoradiographic study. 619 21

The visual pathways of an albino green monkey have been studied electrophysiologically and by autoradiographic methods. The monkey had a white coat and pink eyes; it had a strabismus and a nystagmus. When comparisons were made with normal macaque and green monkeys, several abnormalities could be defined. In the retina there was no foveal pit. A whole mount preparation showed a central area of high ganglion cell density in which the ganglion cells were significantly larger than the most central ganglion cells of a normal monkey. More peripheral retinal areas showed an apparently normal distribution of ganglion cell sizes and packing densities. Within the optic tract the number of uncrossed retinofugal fibers was less than normal, the part of the tract that represents central vision showing almost no uncrossed component. The uncrossed input to the lateral geniculate nucleus and to the superior colliculus was similarly reduced. Regions normally receiving ipsilateral afferents from the central retina were innervated exclusively by crossed afferents. The pathways to the magnocellular geniculate layers showed a more extensive abnormality than did the pathways to the parvicellular layers. Not only were the afferents to the geniculate layers abnormal, but the laminar pattern in the nucleus was also clear than normal in some parts of the nucleus, and there were a number of abnormal laminar fusions. Within the visual cortex it was possible to demonstrate a normal mapping of the contralateral visual field through the contralateral nasal retina and through the peripheral parts of the ipsilateral temporal retina. The central parts of the temporal retina mapped abnormally in the contralateral visual cortex, so that there was a monocular map of the central parts of the visual field forming as a mirror reversal of the normal map. The normal map of the contralateral hemifield formed columns that alternated with the abnormal map of the ipsilateral hemifield. The peripheral parts of the visual field were represented as ocular dominance columns, demonstrable electrophysiologically and also by the transneuronal transport of 3H-proline.
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PMID:Abnormal central visual pathways in the brain of an albino green monkey (Cercopithecus aethiops). 633 Jan 79

We describe a new mitochondrial DNA mutation in a male infant who presented clinical and magnetic resonance imaging features of Leigh syndrome and died at the age of 9 mo. The patient's development was reportedly normal in the first months of life. At the age of 5 mo, he presented severe generalized hypotonia, nystagmus, and absent eye contact. Laboratory examination showed increased lactate and pyruvate in both serum and cerebrospinal fluid. Brain magnetic resonance imaging revealed multiple necrotic lesions in the basal ganglia, brain stem, and thalamus. Muscle histopathology was unremarkable, whereas respiratory chain enzyme analysis revealed a severe complex I deficiency. The patient died after an acidotic coma at age 9 mo. Sequence analysis of the entire mtDNA disclosed a new T10158C mutation with variable tissue heteroplasm (muscle: 83%; blood: 48%). The mutation was undetectable in the blood of his unaffected mother. The transition changes a serine residue into a proline, in a highly conserved region of the NADH dehydrogenase subunit 3 (ND3). This is the first description of a mitochondrial ND3 gene in Leigh syndrome with early lethality.
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PMID:A new mitochondrial DNA mutation in ND3 gene causing severe Leigh syndrome with early lethality. 1476 13

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelinating disorder resulting from mutation of the proteolipid protein gene (PLP1). Clinical features of PMD include progressive psychomotor developmental delay, nystagmus, spastic quadriplegia, dystonia, and cerebellar ataxia. PMD is clinically classified into three subtypes according to the severity of the disease: connatal, transitional, and classic forms. Patients with PMD have been identified with duplication, point mutations, and deletion of PLP1. In addition, spastic paraplegia 2 (SPG2) is allelic to PMD and typically caused by missense mutations in the second extracellular domain of PLP1 or in the PLP1-specific region that is spliced out during formation of the DM20 isoform. The authors describe a Korean boy diagnosed with SPG2 caused by a mutation that results in a Pro215Leu substitution in the second extracellular domain. Analysis of phenotypes resulting from mutations affecting PLP1 has been valuable in identifying functional domains of this still incompletely understood major myelin protein. Null mutations and mutations affecting the PLP1-specific domain cause peripheral neuropathy. The PLP1-specific domain also is important in the long-term maintenance of axonal integrity. This patient's phenotype was relatively mild, in contrast with other mutations at position 215 of PLP1 that cause severe PMD. One of these severe mutations is also a missense mutation substituting an aliphatic residue, alanine, for proline. The distinct severity difference between the Pro215Leu and Pro215Ala substitutions suggests that this region of the protein is very sensitive to subtle structural changes and likely plays a critical role in PLP1 function.
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PMID:A case of complicated spastic paraplegia 2 due to a point mutation in the proteolipid protein 1 gene. 1545 Jul 75

Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C>G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The amino-acid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation.
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PMID:Autosomal-dominant nystagmus, foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation. 2394 4

Oculoleptomeningeal amyloidosis is a rare manifestation of hereditary transthyretin (TTR) amyloidosis. Here, we present the first case of leptomeningeal amyloidosis associated with the TTR variant Leu12Pro mutation in an African patient. A 43-year-old right-handed Nigerian man was referred to our centre with rapidly progressive neurological decline. He presented initially with weight loss, confusion, fatigue, and urinary and erectile dysfunction. He then suffered recurrent episodes of slurred speech with right-sided weakness. He went on to develop hearing difficulties and painless paraesthesia. Neurological examination revealed horizontal gaze-evoked nystagmus, brisk jaw jerk, increased tone, brisk reflexes throughout and bilateral heel-shin ataxia. Magnetic resonance imaging showed extensive leptomeningeal enhancement. Cerebrospinal fluid analysis showed a raised protein of 6.4 g/dl. Nerve conduction studies showed an axonal neuropathy. Echocardiography was characteristic of cardiac amyloid. TTR gene sequencing showed that he was heterozygous for the leucine 12 proline mutation. Meningeal and brain biopsy confirmed widespread amyloid angiopathy. TTR amyloidosis is a rare cause of leptomeningeal enhancement, but should be considered if there is evidence of peripheral or autonomic neuropathy with cardiac or ocular involvement. The relationship between different TTR mutations and clinical phenotype, disease course, and response to treatment remains unclear.
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PMID:Oculoleptomeningeal Amyloidosis associated with transthyretin Leu12Pro in an African patient. 2548 73

Mitochondrial NAD kinase deficiency (NADK2D, OMIM #615787) is a rare autosomal recessive disorder of NADPH biosynthesis that can cause hyperlysinemia and dienoyl-CoA reductase deficiency (DECRD, OMIM #616034). NADK2 deficiency has been reported in only three unrelated patients. Two had severe, unremitting disease; one died at 4 months and the other at 5 years of age. The third was a 10 year old female with CNS anomalies, ataxia, and incoordination. In two cases mutations in NADK2 have been demonstrated. Here, we report the fourth known case, a 15 year old female with normal intelligence and a mild clinical and biochemical phenotype presumably without DECRD. Her clinical symptoms, which are now stable, became evident at the age of 9 with the onset of decreased visual acuity, bilateral optic atrophy, nystagmus, episodic lower extremity weakness, peripheral neuropathy, and gait abnormalities. Plasma amino acid levels were within normal limits except for mean lysine and proline levels that were 3.7 and 2.5 times the upper limits of normal. Whole exome sequencing (WES) revealed homozygosity for a g.36241900 A>G p. Met1Val start loss mutation in the primary NADK2 transcript (NM_001085411.1) encoding the 442 amino acid isoform. This presumed hypomorphic mutation has not been previously reported and is absent from the v1000GP, EVS, and ExAC databases. Our patient's normal intelligence and stable disease expands the clinical heterogeneity and the prognosis associated with NADK2 deficiency. Our findings also clarify the mechanism underlying NADK2 deficiency and suggest that this disease should be ruled out in cases of hyperlysinemia, especially those with visual loss, and neurological phenotypes.
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PMID:Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant. 2938 19


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