Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal-dominant neurodegenerative disease characterized by variable clinical phenotypes. Its characteristic clinical manifestations include ataxia, choreoathetotic movements, seizures, myoclonus and dementia, but cervical dystonia has been rarely reported. Here we report a family with DRPLA who presented with cervical dystonia. The proband was a 66-year-old woman. Cervical dystonia was the initial and the most prominent symptom, and mild cerebellar signs and choreic movements were also observed. DNA analysis revealed expanded trinucleotide repeats within the DRPLA gene. The daughter of the proband, a 29-year-old woman, also had cervical dystonia for 3 years. Cranial magnetic resonance imaging showed a mild atrophy of the brainstem and the cerebellum in both of these patients. DRPLA should be considered in the differential diagnosis of patients presenting with cervical dystonia.
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PMID:Cervical dystonia in dentatorubral-pallidoluysian atrophy. 1295 64

We report a 23-year-old man with mitochondrial encephalomyopathy. At 21 years of age, he noted speech distubance. Since his dysarthria did not improve thereafter, he was admitted to our hospital. On admission, he showed mild gynecomastia. Neurological examination revealed mild decrease in performance IQ in WAIS-R, mild scanning speech, mild left hearing disturbance, mild to moderate muscle weakness in proximal four extremities, mild bilateral limb ataxia, and mild to moderate truncal ataxia. While, no brisk deep tendon reflex, pathological reflex, aberrant muscle tonus, sensory disturbance, retinopathy, myoclonus or autonomic disorder was found. Serum levels of lactate (23.2 mg/dl, normal<18.7) and pyruvate (1.23 mg/dl, normal<0.94) were elevated, and serum lactate levels were markedly elevated (118.1 mg/dl) after 15-minute exercise (15 Watts/minute). CSF levels of lactate (31.2 mg/dl, normal<12.5) and pyruvate (1.48 mg/dl, normal<0.75) were also elevated. Head MRI showed mild cerebral and cerebellar atrophy, but 1H-MRS showed no lactate peak. Moreover, muscle biopsy from left biceps muscle showed lots of ragged-red fibers, and he was thus diagnosed as having mitochondrial encephalomyopathy. However, nt3243 mutation of mitochondria DNA was not present. Next, we confirmed gynecomastia by mammography, and checked serum levels of estrogens. Mildly decreased estradiol (19.9 pg/ml, normal, 20-59), normal estrone (24.0 pg/ml, normal<30.0) and mildly increased estriol (6.03 pg/ml, normal<5.0) were found. While, the serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were all within normal limits. Since the steroid hormone synthesis system and hypothalamus-pituitary system seem to be normal, 16alpha-hydroxylase that converts estradiol to estriol may be upregulated. While, aromatase (P-450arom) is well known to convert androgens to estrogens. In addition, 16alpha-hydroxylase and P-450arom convert DHEA-S to estriol. Since it is recently reported that P-450arom is considerably expressed in muscle tissues as well as fat tissues and that muscle tissue may be a major organ to produce estrogens in men and postmenopausal women, estriol production may be increased in the present patient's muscle. Although hypogonadism due to hypothalamus-pituitary disorders was sometimes reported, there have been no reports that suggest an increased estrogen production in skeletal muscles in mitochondrial encephalomyopathies. Recently, estrogen has been known to protect muscle fibers from oxidative damages due to exercise. Thus, it is of potential that estrogens increased locally in muscle tissues of the patients with mitochondrial encephalomyopathies protect muscle fibers from oxidative damage due to mitochondrial dysfunction.
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PMID:[A patient with mitochondrial encephalomyopathy presenting gynecomastia with elevation of serum estriol level]. 1528 12

Progressive myoclonus epilepsy (PME) has a number of causes, of which Unverricht-Lundborg disease (ULD) is the most common. ULD has previously been mapped to a locus on chromosome 21 (EPM1). Subsequently, mutations in the cystatin B gene have been found in most cases. In the present work we identified an inbred Arab family with a clinical pattern compatible with ULD, but mutations in the cystatin B gene were absent. We sought to characterize the clinical and molecular features of the disorder. The family was studied by multiple field trips to their town to clarify details of the complex consanguineous relationships and to personally examine the family. DNA was collected for subsequent molecular analyses from 21 individuals. A genome-wide screen was performed using 811 microsatellite markers. Homozygosity mapping was used to identify loci of interest. There were eight affected individuals. Clinical onset was at 7.3 +/- 1.5 years with myoclonic or tonic-clonic seizures. All had myoclonus that progressed in severity over time and seven had tonic-clonic seizures. Ataxia, in addition to myoclonus, occurred in all. Detailed cognitive assessment was not possible, but there was no significant progressive dementia. There was intrafamily variation in severity; three required wheelchairs in adult life; the others could walk unaided. MRI, muscle and skin biopsies on one individual were unremarkable. We mapped the family to a 15-megabase region at the pericentromeric region of chromosome 12 with a maximum lod score of 6.32. Although the phenotype of individual subjects was typical of ULD, the mean age of onset (7.3 years versus 11 years for ULD) was younger. The locus on chromosome 12 does not contain genes for any other form of PME, nor does it have genes known to be related to cystatin B. This represents a new form of PME and we have designated the locus as EPM1B.
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PMID:A new clinical and molecular form of Unverricht-Lundborg disease localized by homozygosity mapping. 1563 28

Direct genomic DNA sequencing fails to detect epsilon-sarcoglycan (SGCE) mutations in up to 30% of familial myoclonus-dystonia (M-D) cases. We identified novel large heterozygous deletions of SGCE exon 5 or exon 6 in two M-D pedigrees. Like nonsense mutations, exon rearrangements result in the generation of premature stop codons downstream of the deleted exon. SGCE exon dosage assays may identify additional families with SGCE mutation and thus reduce "genetic heterogeneity."
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PMID:Myoclonus-dystonia due to genomic deletions in the epsilon-sarcoglycan gene. 1624 Mar 55

Cerebellar syndromes and radiologic cerebellar atrophy after hyperpyrexia have occasionally been reported, mostly in neuroleptic malignant syndromes, but neuropathologic studies are extremely rare. We studied 3 patients (a 74-year-old woman, a 63-year-old man, and an 80-year-old man) who had heat stroke during heat waves in France. One patient had generalized seizures and died 28 hours after admission. The other patients survived one month and 2 months after admission; both had palatal myoclonus, and in one case, magnetic resonance imaging showed high signal intensity in the cerebral peduncles. The main neuropathology in the 3 cases was severe diffuse loss of Purkinje cells associated with heat shock protein 70 expression by Bergmann glia. In situ end labeling was negative in surviving Purkinje cells, suggesting that the mechanism of neuronal death was not apoptosis. Degeneration of Purkinje cells axons resulted in myelin pallor of the white matter of the folia and of the hilum of the dentate nuclei. DNA internucleosomal breakages were identified by in situ end labeling in the dentate nuclei and centromedian nuclei of the thalamus and were associated with degeneration of the cerebellar efferent pathways: superior cerebellar peduncles, decussation of the superior cerebellar peduncles (Wernekinck commissure), and dentatothalamic tract. These findings suggest that the mechanisms of neuronal death in the dentate nuclei and centromedian nuclei of the thalamus was different from that in Purkinje cells and more likely resulted from deafferentation. Ammon's horn and other areas susceptible to hypoxia were spared. These observations confirm the selective vulnerability of Purkinje cells to heat-induced injury and involvement of the cerebellar efferent pathways in palatal myoclonus.
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PMID:Brain damage after heat stroke. 1625 91

Huntington disease is a dominantly inherited, neurodegenerative disorder, usually with onset in the fourth to fifth decade of life but in a small proportion of patients before the age of 20 years. The early-onset form, juvenile Huntington disease, is clinically different from that of more common adult-onset forms and includes cognitive decline, parkinsonism, myoclonus, and seizures. We report a case of a boy with juvenile Huntington disease with a very early age at disease onset (3 years). The suspected clinical diagnosis was confirmed by DNA analysis, which revealed (CAG)(n) expansion into the range characteristic of juvenile Huntington disease (95 repeats). The clinical course of the disease was typical for the juvenile form of Huntington disease, but the diagnosis was not so obvious because there was no history of any neurodegenerative disorder in the family. The child died at the age of 11 years. The detailed neuropathologic investigations performed postmortem showed the characteristic features of Huntington disease. As the patient's de novo mutation was very unlikely to occur, genetic counseling and the possibility of predictive testing were proposed to the family. Indirect molecular data indicate the familial character of the disease, with strong anticipation of transmission.
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PMID:Huntington disease in a 9-year-old boy: clinical course and neuropathologic examination. 1715 1

Mitochondrial encephalopathies are a group of diseases that have as their pathogenic basis an alteration of the mitochondrial DNA (mtDNA). The MELAS phenotype (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) has been related to mutation A3243G in approximately 80% of the cases reported. MERRF (epilepsy myoclonus with ragged red fibers) has been related to mutation A8344G and A8566G of tRNA Lys. We report the case of a 7 months-old female with early clinical signs of encephalopathy associated to the A3243G mutation. Laboratory tests showed lactic acidosis and the EEG pattern was compatible with an encephalopathic process. The infant was treated with ACTH during one month, with clinical and electroencephalographic improvements. Currently, she is receiving treatment with B-vitamins, L-Carnitine and urinary alkalizing agents. It is concluded that an analysis of mtDNA must be made in infants who present convulsions, delay in their psychomotor development, lactic acidosis and an EEG pattern compatible with an encephalopathy, to rule out a mitochondrial disease.
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PMID:[Infantile encephalopathy associated with the MELAS A3243G mutation. Case report]. 1759 46

Because of the occurrence of different types of mutations, comprehensive genetic testing for Parkinson's disease (PD), dopa-responsive dystonia (DRD), and myoclonus-dystonia (M-D) should include screening for small sequence changes and for large exonic rearrangements in disease-associated genes. In diagnostic and research settings, the latter is frequently omitted or performed by laborious and expensive quantitative real-time PCR (qPCR). Our study aimed to evaluate the utility of a novel method, multiplex ligation-dependent probe amplification (MLPA), in molecular diagnostics of movement disorders. We have analyzed, by MLPA, genomic DNA from 21 patients affected with PD, DRD, or M-D, in which the presence of exon rearrangement(s) (n = 20) or of a specific point mutation (detectable by MLPA, n = 1) had been established previously by qPCR or sequencing. In parallel, we have studied, in a blinded fashion, DNA from 49 patients with an unknown mutational status. Exon rearrangements were evident in 20 samples with previously established mutations; in the 21st sample the known specific point mutation was detected. We conclude that MLPA represents a reliable method for large-scale and cost-effective gene dosage screening of various movement disorders genes. This finding reaches far beyond a simple technical advancement and has two major implications: (1) By improving the availability of comprehensive genetic testing, it supports clinicians in the establishment of a genetically defined diagnosis; (2) By enabling gene dosage testing of several genes simultaneously, it significantly facilitates the mutational analysis of large patient and control populations and thereby constitutes the prerequisite for meaningful phenotype-genotype correlations.
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PMID:Rapid and reliable detection of exon rearrangements in various movement disorders genes by multiplex ligation-dependent probe amplification. 1767 14

Huntington disease-like 2 (HDL2) is a neurodegenerative disorder caused by an expansion of a CTG repeat in the junctophilin-3 gene (JPH3). A limited number of HDL2 families have been reported, all of apparently Black African ancestry. We report on a South African family that presented with progressive dementia and a movement disorder affecting numerous family members. Genotyping of the JPH3 CTG repeat revealed pathogenic expansions in three affected individuals. Whereas HDL2 is thought to be clinically indistinguishable from Huntington disease (HD), 2 of the patients in this study presented with clinical symptoms that differed substantially from HD; one had myoclonus and the other had Parkinsonism. Moreover, brain magnetic resonance imaging scans of these patients showed imaging features atypical for HD. Mitochondrial DNA and Y-chromosome DNA analysis on a family member showed that his maternal and paternal ancestries are typical of that found among the South African mixed ancestry or colored population. A difference in the distribution of CTG repeats between Caucasian and Black individuals was detected. We conclude that the phenotype of HDL2 is broad and can differ from that of typical HD. The diagnosis therefore should be considered in a wide spectrum of neuropsychiatric and abnormal movement presentations.
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PMID:A South African mixed ancestry family with Huntington disease-like 2: clinical and genetic features. 1770 69

Myoclonus-dystonia (M-D) is an autosomal-dominant movement disorder caused by mutations in SGCE. We investigated the frequency and type of SGCE mutations with emphasis on gene dosage alterations and explored the associated phenotypes. We tested 35 M-D index patients by multiplex ligation-dependent probe amplification (MLPA) and genomic sequencing. Mutations were found in 26% (9/35) of the cases, all but three with definite M-D. Two heterozygous deletions of the entire SGCE gene and flanking DNA and a heterozygous deletion of exon 2 only were detected, accounting for 33% (3/9) of the mutations found. Both large deletions contained COL1A2 and were additionally associated with joint problems. Further, we discovered one novel small deletion (c.771_772delAT, p.C258X) and four recurrent point mutations (c.289C>T, p.R97X; c.304C>T, p.R102X; c.709C>T, p.R237X; c.1114C>T, p.R372X). A Medline search identified 22 articles on SGCE mutational screening. Sixty-four unrelated M-D patients were described with 41 different mutations. No genotype-phenotype association was found, except in patients with deletions encompassing additional genes. In conclusion, a rigorous clinical preselection of patients and careful accounting for non-motor signs should precede mutational tests. Gene dosage studies should be included in routine SGCE genetic testing.
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PMID:Myoclonus-dystonia: significance of large SGCE deletions. 1820 93


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