Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After our initial discovery of reduced expression of several subunits of the GABA(A) receptor in two different animal models for fragile X syndrome, a frequent form of inherited mental retardation, we analyzed further components of the GABAergic pathway. Interestingly, we found a down regulation of many additional elements of the GABA signalling system, strengthening our hypothesis of involvement of the GABAergic pathway in the pathophysiology of fragile X syndrome. This is of special interest with regard to new therapeutic opportunities for treatment of this disorder. Remarkably, under expression was predominantly observed in cortex, although some elements of the GABAergic system that are expressed presynaptically or in the glial cells were also down regulated in the cerebellum. Additionally, we assessed the GABAergic system in expanded CGG-repeat mice, a model for fragile X associated tremor/ataxia syndrome (FXTAS). This late onset neurodegenerative disorder occurs in carriers of the fragile X premutation (55-200 CGG repeats) and is completely distinct (from both clinical and molecular pathogenic perspectives) from the neurodevelopmental disorder fragile X syndrome. Here we found upregulation of many components of the GABAergic system in cerebellum, but not in cortex. This finding is consistent with the cerebellar phenotype of FXTAS patients and has implications for the mechanism causative of differential gene expression.
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PMID:Expression of the GABAergic system in animal models for fragile X syndrome and fragile X associated tremor/ataxia syndrome (FXTAS). 1907 Jun 6

The CGG-repeat present in the 5'UTR of the FMR1 gene is unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In fragile X patients, a repeat length exceeding 200 CGGs (full mutation: FM) generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. The gene product FMRP is involved in regulation of transport and translation of certain mRNA in the dendrite, thereby affecting synaptic plasticity. This is central to learning and memory processes. The absence of FMRP seen in FM is the cause of the mental retardation seen in fragile X patients. The premutation (PM) is defined as 55-200 CGGs. Female PM carriers are at risk of developing primary ovarian insufficiency. Recently it was discovered that elderly PM carriers might develop a progressive neurodegenerative disorder called fragile X-associated tremor/ataxia syndrome. Although arising from the mutations in the same gene, distinct mechanisms lead to fragile X syndrome (absence of FMRP) and FXTAS (toxic RNA gain of function). The pathogenic mechanisms thought to underlie these disorders are discussed, with a specific emphasis on FXTAS. This review gives insight on the implications of all possible repeat length categories seen in fragile X families.
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PMID:The FMR1 gene and fragile X-associated tremor/ataxia syndrome. 1910 4

Autosomal recessive hereditary spastic paraplegia (AR HSP) with thin corpus callosum (TCC) is a rare neurodegenerative disorder often caused by mutations in the gene encoding for spatacsin at the SPG11 locus on chromosome 15q. The disease is characterized by progressive spastic paraparesis and mental retardation which occur during the first two decades of life and frequently with peripheral neuropathy. Brain magnetic resonance imaging (MRI) reveals typical TCC with periventricular white matter changes. We describe two patients, of Turkish descent, from the same consanguineous family and affected with SPG11 in association with unusual early-onset parkinsonism. Parkinsonism occurred during the very early stages of SPG11 in both patients, being in one the inaugural symptom of the disease presented as a resting tremor with akinesia, rigidity and expressing an initial moderate levodopa-response that progressively weakened. The second patient presented a resting tremor with mild akinesia and no levodopa-response. Both patients were affected with progressive spastic paraparesis which had initially occurred at 15 and 12 years of age, respectively, in association with mild mental retardation and an axonal polyneuropathy. TCC with periventricular white matter changes (PWMC) was evident by MRI and (123)I-ioflupane SPECT was abnormal. Genetic analysis detected for both patients a new c.704_705delAT, p.H235RfsX12 homozygous mutation in SPG11. This report provides evidence that parkinsonism may initiate SPG11-linked HSP TCC and that SPG11 may cause juvenile parkinsonism.
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PMID:SPG11 spastic paraplegia. A new cause of juvenile parkinsonism. 1922 11

Carriers of expanded, but unmethylated, premutation alleles of the fragile X mental retardation gene are at risk for a late-onset tremor/ataxia syndrome, mostly affecting men over age 50. However, the general neuropsychological and neurobehavioral impact of carrying a premutation allele in younger adults not affected by the tremor/ataxia syndrome remains unclear. Past studies have utilized varying study designs resulting in inconsistent conclusions. To better understand the current evidence of the influence of the premutation on such traits in adult carriers, we reviewed the literature and identified 16 studies that met conservative inclusion criteria, including molecular measures of the fragile X mental retardation gene CGG triplet repeat length and standard measures of neurobehavioral and neurocognitive phenotypes. A review of these studies is presented to assess the evidence for possible premutation-associated neuropsychological deficits among adult men and women who do not meet diagnostic criteria of the tremor/ataxia syndrome. Results of these studies, and possible reasons for inconsistent conclusions, are discussed. The primary conclusion from this review is the need for further research using a standard protocol in a large multisite project to ensure the necessary sample size.
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PMID:Is there evidence for neuropsychological and neurobehavioral phenotypes among adults without FXTAS who carry the FMR1 premutation? A review of current literature. 1926 46

Galactosemia, an inborn neurometabolic disorder, results from an aberrant galactose metabolism due to the deficiency of serum galactose-1-phosphate uridyltransferase activity. It manifests in the central nervous system in the form of hypotonia, seizures, mental retardation, tremor, ataxia, and progressive cerebellar as well as extrapyramidal features. To the best of our knowledge, chorea due to galactosemia has not been reported in infancy.
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PMID:Galactosemia with chorea--an unusual presentation. 1939 Oct 11

The FXTAS syndrome (Fragile X-associated tremor/ataxia syndrome) is a specific neurodegenerative syndrome affecting subjects carrying a premutation of the FMR1 (fragile X mental retardation 1) gene. It affects mainly men with the premutation and aged more than 50 years. This syndrome is separate and distinct from the fragile X syndrome. The FXTAS syndrome remains underestimated today. It should be considered in patients older than 50 years with tremors and cerebellar ataxia, especially when Parkinson disease or cognitive disorders are present or when there is a family history of infertility, early menopause, or mental retardation. In these patients, hyperintense signals of mid-cerebellar peduncle images on T2 and FLAIR MRI justify genetic testing for the FMR1 premutation.
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PMID:[Tremor/ataxia syndrome related to Fragile X premutation]. 1941 33

We describe a child with epilepsy associated with double-cortex syndrome in whom vagus nerve stimulation (VNS) generated parkinsonian symptoms. A 13-year-old girl presented with refractory secondary generalized epilepsy from the age of 6 years and mental retardation. Her electroencephalography (EEG) showed diffuse polyspike and wave discharges. Magnetic resonance imaging (MRI) showed double-cortex syndrome. She was submitted to extended callosal section at the age of 10 years, which yielded 50% seizure frequency reduction. She was submitted to VNS by the age of 12 years. As stimulation intensity was increased, there was appearance of extrapyramidal symptoms: She developed bilateral tremor and rigidity, and gait and postural disturbance. All symptoms disappeared 7-10 days after VNS was turned off. Several attempts to reactivate VNS led to the same results. During the periods when VNS was on she presented with marked seizure frequency reduction. This is the first report of a clinically evident direct effect of VNS on the basal ganglia.
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PMID:Parkinsonism induced by VNS in a child with double-cortex syndrome. 1967 51

The gene responsible for Fragile X syndrome, fragile X mental retardation-1 (FMR1), contains an unstable sequence of CGG trinucleotide repeats in its promoter region. Expansions of >200 trinucleotide repeats are considered full mutations and typically lead to abnormal methylation of the region resulting in loss of FMR1 expression. Males with loss of FMR1 protein are expected to be affected by Fragile X syndrome while females may or may not clinically manifest features of the condition. The protocols in this unit outline the complementary use of polymerase chain reaction (PCR) and methylation-sensitive Southern blot hybridization to accurately measure trinucleotide repeat size and methylation status. These protocols are also used to evaluate CGG repeat size in two adult-onset conditions known for their association with FMR1 premutation alleles, Fragile X Tremor/Ataxia (FXTAS) syndrome and Premature Ovarian Failure (POF).
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PMID:Molecular analysis of Fragile X syndrome. 1980 93

Women with fragile X mental retardation (FMR1) gene premutations (55-200 CGG repeats) were until recently believed to be unaffected. It is now known that up to 8% of older female FMR1 premutation carriers develop fragile X-associated tremor/ataxia syndrome (FXTAS). Female carriers may also develop primary ovarian insufficiency, thyroid disease, hypertension, seizures, peripheral neuropathy, and fibromyalgia. We present a 60-year-old woman with FMR1 premutation who had depression, anxiety, and conversion disorder with seizures. The FMR1 premutation with its associated mRNA toxicity is postulated as an underlying neurobiological mechanism of conversion symptoms, through functional and structural neural dysconnectivity.
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PMID:Conversion disorder in women with the FMR1 premutation. 1984 97

Following the discovery of two disorders associated with premutation alleles of the fragile X mental retardation gene (FMR1), primary ovarian insufficiency [fragile X-associated primary ovarian insufficiency (FXPOI)] and a tremor/ataxia syndrome [fragile X-associated tremor/ataxia disorder (FXTAS)], numerous studies have examined other potential co-morbid conditions, including neuropsychological deficits. Here, the frequency of self-reported diagnoses obtained through medical history interviews from FMR1 premutation carriers and non-carriers aged 18-50 were analyzed. Study subjects included 537 women, 334 of whom carry the premutation and 151 men, 37 of whom carry the premutation. Men with the premutation did not report any medical conditions at higher rates compared with non-carriers, controlling for age, ethnicity/race, and household income. Women with the premutation reported mental health disorders [i.e. attention deficit hyperactivity disorder (ADHD), anxiety, depression] significantly more often than non-carriers. However, after adjusting for covariates, these increased rates were not statistically significant. Additional follow-up analyses examined the consequence of ovarian dysfunction as a cause of co-occurring conditions. Women with an indication of ovarian insufficiency (i.e. irregular cycles) reported higher rates of thyroid problems and depression/anxiety. Because only women, not men, reported these conditions more often, the relationship between FXPOI and hormone irregularities in women should be explored for a potential link with the increase in the reported medical conditions.
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PMID:Co-occurring diagnoses among FMR1 premutation allele carriers. 2005 84


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