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)

Thyroid hormones are iodothyronines that control growth and development, as well as brain function and metabolism. Although thyroid hormone deficiency can be caused by defects of hormone synthesis and action, it has not been linked to a defect in cellular hormone transport. In fact, the physiological role of the several classes of membrane transporters remains unknown. We now report, for the first time, mutations in the monocarboxylate transporter 8 (MCT8) gene, located on the X chromosome, that encodes a 613-amino acid protein with 12 predicted transmembrane domains. The propositi of two unrelated families are males with abnormal relative concentrations of three circulating iodothyronines, as well as neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects. These findings establish the physiological importance of MCT8 as a thyroid hormone transporter.
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PMID:A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. 1466 Nov 63

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

We herein report the findings of a 2-year-6-month-old boy, who had been experiencing monocular pendular nystagmus, strabismus, and episodic eye deviation nystagmus, intractable dystonia and apneic attack which all began when he was 2 days of age. He underwent a complete blood count test, blood chemistry test, analysis of amino acids in the blood and urine, analysis of pyruvate/lactate in blood and cerebrospinal fluid, head computed tomography and magnetic resonance imaging and no abnormal results were identified. His attacks were resistant to multiple antiepileptic and dopaminergic drugs. He showed transient left and/or right hemiplegia after nystagmus, dystonia and/or apneic attacks at 8-months of age with retardation in intelligence. We diagnosed him to have alternating hemiplegia of childhood (AHC). We were unsure how to deal with his attacks after he was discharged from the hospital, however, resuscitation with the ambu bag by his mother at home and the intravenous infusion of diazepam or thiamylal at the hospital together was proven to be an effective method for treating his severe apneic attacks. The effect of diazepam and amantadine on these attacks was transient, however, the administration of flunarizine with amantadine resulted in an improvement in his attacks. We therefore consider the administration of flunarizine to be essential for the effective treatment of AHC in this case.
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PMID:[A boy with nystagmus, refractory dystonia and apneic attack due to alternating hemiplegia of childhood]. 1763 86

SCA17 is a rare type of autosomal dominant spinocerebellar ataxia caused by a CAG/CAA expansion in the gene encoding the TATA-binding protein (TBP). We screened for triplet expansion in the TBP gene 110 subjects with progressive cerebellar ataxia and 94 subjects with Huntington-like phenotype negative at specific molecular tests. SCA17 mutation-positive subjects were found in both groups of patients. Expanded alleles with > or = 44 CAG/CAA repeats were identified in 11 individuals and in 4 non-symptomatic relatives. Eleven de novo diagnosed patients and four patients previously reported underwent extensive clinical, neuroradiological and oculographic examination. Cerebellar signs and symptoms were present in all cases; 80% of the patients had mild to severe cognitive deficits; 66% of patients showed choreic movements; pyramidal signs, bradykinesia and dystonia were observed in approx 50% of the cases. MRI demonstrated cortical and cerebellar atrophy in all patients, whereas neurophysiological examination excluded signs of peripheral nervous system involvement. Oculographic examinations were performed in 9 out of 15 patients and showed a distinct pattern of oculomotor abnormalities, characterized by impairment of smooth pursuit, defects in the saccade accuracy, normal saccade velocity, hyperreflexia of vestibuloocular reflexes, and absence of nystagmus. In summary, this study presents one of the largest series of SCA17 patients in Europe. In our group of patients, SCA17 represents the third most frequent SCA genotype. Our clinical data confirm the large variability in SCA17 phenotypic presentation, and indicate that a peculiar combination of neuroradiological, electrophysiological and oculomotor findings is recognizable in SCA17.
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PMID:Spinocerebellar ataxia type 17 (SCA17): oculomotor phenotype and clinical characterization of 15 Italian patients. 1793 76

Clinical lateralizing signs are the phenomena which can unequivocally refer to the hemispheric onset of epileptic seizures. They can improve the localization of epileptogenic zone during presurgical evaluation, moreover, their presence can predict a success of surgical treatment. Primary sensory phenomena such as visual aura in one half of the field of vision or unilateral ictal somatosensory sensation always appear on the contralateral to the focus. Periictal unilateral headache, although it is an infrequent symptom, is usually an ipsilateral sign. Primary motor phenomena like epileptic clonic, tonic movements, the version of head ubiquitously appear contralateral to the epileptogenic zone. Very useful lateralization sign is the ictal hand-dystonia which lateralizes to the contralateral hemisphere in nearly 100%. The last clonus of the secondarily generalized tonic-clonic seizure lateralizes to the ipsilateral hemisphere in 85%. The fast component of ictal nystagmus appears in nearly 100% on the contralateral side of the epileptic focus. Vegetative symptoms during seizures arising from temporal lobe such as spitting, nausea, vomiting, urinary urge are typical for seizures originating from non-dominant (right) hemisphere. Ictal pallor and cold shivers are dominant hemispheric lateralization signs. Postictal unilateral nose wiping refers to the ipsilateral hemispheric focus compared to the wiping hand. Ictal or postictal aphasia refers to seizure arising from dominant hemisphere. Intelligable speech during complex partial seizures appears in non-dominant seizures. Automatism with preserved consciousness refers to the seizures of non-dominant temporal lobe.
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PMID:[Brain lateralization and seizure semiology: ictal clinical lateralizing signs]. 1876 78

Leigh syndrome (also termed subacute, necrotizing encephalopathy) is a devastating neurodegenerative disorder, characterized by almost identical brain changes, e.g., focal, bilaterally symmetric lesions, particularly in the basal ganglia, thalamus, and brainstem, but with considerable clinical and genetic heterogeneity. Clinically, Leigh syndrome is characterized by a wide variety of abnormalities, from severe neurologic problems to a near absence of abnormalities. Most frequently the central nervous system is affected, with psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure. Some patients also present with peripheral nervous system involvement, including polyneuropathy or myopathy, or non-neurologic abnormalities, e.g., diabetes, short stature, hypertrichosis, cardiomyopathy, anemia, renal failure, vomiting, or diarrhea (Leigh-like syndrome). In the majority of cases, onset is in early childhood, but in a small number of cases, adults are affected. In the majority of cases, dysfunction of the respiratory chain (particularly complexes I, II, IV, or V), of coenzyme Q, or of the pyruvate dehydrogenase complex are responsible for the disease. Associated mutations affect genes of the mitochondrial or nuclear genome. Leigh syndrome and Leigh-like syndrome are the mitochondrial disorders with the largest genetic heterogeneity.
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PMID:Leigh and Leigh-like syndrome in children and adults. 1880 59

Electronistagmography has been performed in a vestibular function study of patients with facial dyskinesias - blepharospasm and facial hemispasm - before and after treatment with botulotoxin type A (dysport). A comparison groups included patients with myasthenia, functional dyskinesias, Greffe myodystrophy and healthy people. The method was applied for hyperkinesis objectification in patients with facial dyskinesias with the high amount of muscles artifacts caused by involuntary contractions of eye orbicular muscle. Ratio of the muscles artifact duration to the duration of investigation designated as the coefficient of eyelids dystonia period was determined. Blefarospasm symptoms were maximal during the gaze abduction and the direct gaze and minimal with eyes closed. The hyperkinesis caused disturbances of the visual-vestibular interaction during sinusoidal head rotations with the gaze fixation on the movable object, the appearance of deformed nystagmus waves with 2-peaks, the dysrhythmia and optokinetic nystagmus asymmetry. The disturbances mentioned above decreased or disappeared after the treatment with dysport. Vestibular disturbances were not revealed in other groups included in the study. The results of this study confirm the correlation between the hyperkinesis duration and the eyeballs position in blepharospasm and support evidence of the involvement of the peripheral factor in the pathogenesis of this disease.
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PMID:[Electronistagmographic characteristics of vestibular function and eyelids dystonia in patients with facial dyskinesias]. 2135 Apr 13

Congential hemifacial spasm is a rare condition that is characterized by the occurrence of paroxysmal hemifacial contractions in neonates. We review the clinical, neurophysiological, neuroimaging, and histopathological findings, as well as the differential diagnosis, therapeutic approach, and outcome of all the described cases. Moreover, we report two new cases including the ictal video-electroencephalography recordings. Hemifacial spasm starts early in life, and is characterized by unilateral, involuntary, irregular tonic or clonic contractions of muscles innervated by the seventh cranial nerve. Hemifacial spasm is associated with eyelid blinking, and sometimes with breathing irregularities, hyperventilation, and/or other neurological manifestations (dystonic movements, nystagmus). Interictal and ictal video-electroencephalography did not reveal epileptiform abnormalities. In all cases, brain magnetic resonance imaging showed a mass involving the cerebellar peduncle, the cerebellar hemisphere, or the floor of the fourth ventricle. The semiology of the paroxysmal attacks is probably due to the activation of cranial nerve nuclei through intralesional hypersynchronous discharges, as shown by the intraoperative recordings and functional brain imaging described in the literature. We point out the importance of identifying such seizures in order to make an early diagnosis of the underlying cerebral lesion.
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PMID:Neonatal hemifacial spasm and fourth ventricle mass. 2254 45

Mitochondrial complex I is the largest multi-protein enzyme complex of the oxidative phosphorylation system. Seven subunits of this complex are encoded by the mitochondrial and the remainder by the nuclear genome. We review the natural disease course and signs and symptoms of 130 patients (four new cases and 126 from literature) with mutations in nuclear genes encoding structural complex I proteins or those involved in its assembly. Complex I deficiency caused by a nuclear gene defect is usually a non-dysmorphic syndrome, characterized by severe multi-system organ involvement and a poor prognosis. Age at presentation may vary, but is generally within the first year of life. The most prevalent symptoms include hypotonia, nystagmus, respiratory abnormalities, pyramidal signs, dystonia, psychomotor retardation or regression, failure to thrive, and feeding problems. Characteristic symptoms include brainstem involvement, optic atrophy and Leigh syndrome on MRI, either or not in combination with internal organ involvement and lactic acidemia. Virtually all children ultimately develop Leigh syndrome or leukoencephalopathy. Twenty-five percent of the patients died before the age of six months, more than half before the age of two and 75 % before the age of ten years. Some patients showed recovery of certain skills or are still alive in their thirties . No clinical, biochemical, or genetic parameters indicating longer survival were found. No clear genotype-phenotype correlations were observed, however defects in some genes seem to be associated with a better or poorer prognosis, cardiomyopathy, Leigh syndrome or brainstem lesions.
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PMID:Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases. 2264 3

Type 2 episodic ataxia (EA2) is the most common subtype among a group of rare hereditary syndromes characterized by recurrent attacks of ataxia. More than 60 mutations and several gene rearrangements due to large deletions in CACNA1A gene have been reported so far for the cause of EA2. Because CACNA1A gene is a large gene containing 47 exons and there is no hot spot mutation, direct sequencing will be a challenge in clinical genetic testing. In this study, we used next generation sequencing technology to identify a novel nonsense mutation of CACNA1A (p.Tyr1957Ter, NP_001120693.1) resulting in truncated protein without 305 amino acids in the c-terminus. Sanger sequencing confirmed the heterozygous mutation of CACNA1A in a Chinese family with 11 affected individuals. Affected individuals experienced recurrent attacks with or without nystagmus, dysarthria, seizure, myokymia, dystonia, weakness, blurred vision, visual field defects, diplopia, migraine, dizziness, nausea and vomiting, sweating and abdominal pain. This is the first report of EA2 in a Chinese family that carries a novel mutation in CACNA1A gene and had abdominal pain as a novel phenotype associated with EA2.
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PMID:Identification of a novel nonsense mutation p.Tyr1957Ter of CACNA1A in a Chinese family with episodic ataxia 2. 2344 Nov 82


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