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)

Fragile X syndrome (an FMR1-related disorder) is the most commonly inherited form of mental retardation. Early physical recognition is difficult, so boys with developmental delay should be strongly considered for molecular testing. The characteristic adult phenotype usually does not develop until the second decade of life. Girls can also be affected with developmental delay. Because multiple family members can be affected with mental retardation and other conditions (premature ovarian failure and tremor/ataxia), family history information is of critical importance for the diagnosis and management of affected patients and their families. This report summarizes issues for fragile X syndrome regarding clinical diagnosis, laboratory diagnosis, genetic counseling, related health problems, behavior management, and age-related health supervision guidelines. The diagnosis of fragile X syndrome not only involves the affected children but also potentially has significant health consequences for multiple generations in each family.
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PMID:Health supervision for children with fragile X syndrome. 2151 20

Classical galactosemia is an autosomal recessive inborn error of metabolism leading to toxic accumulation of galactose and derived metabolites. It presents with acute systemic complications in the newborn. Galactose restriction resolves these symptoms, but long-term complications, such as premature ovarian failure and neurological problems including motor dysfunction, may occur despite adequate treatment. The objective of the current study was to determine the frequency and phenotype of motor problems in adult patients with classical galactosemia. In this cross-sectional study, adult patients with a biochemically confirmed diagnosis of galactosemia attending our clinic were assessed with an interview and neurological examination and their notes retrospectively reviewed. Patients were classified according to the presence/absence of motor dysfunction on examination. Patients with motor dysfunction were further categorized according to the presence/absence of reported motor symptoms. Forty-seven patients were included. Thirty-one patients showed evidence of motor dysfunction including: tremor (23 patients), dystonia (23 patients), cerebellar signs (6 patients), and pyramidal signs (4 patients). Tremor and dystonia were often combined (16 patients). Thirteen patients reported motor symptoms, with 8 describing progressive worsening. Symptomatic treatment was effective in 4 of 5 patients. Nonmotor neurological features (cognitive, psychiatric, and speech disorders) and premature ovarian failure were more frequent in patients with motor dysfunction. Motor dysfunction is a common complication of classical galactosemia, with tremor and dystonia the most frequent findings. Up to one third of patients report motor symptoms and may benefit from appropriate treatment. Progressive worsening is not uncommon and may suggest ongoing brain damage in a subset of patients.
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PMID:Movement disorders in adult patients with classical galactosemia. 2340 Aug 15

Male premutation carriers presenting between 55 and 200 CGG repeats in the Fragile-X-associated (FMR1) gene are at risk of developing Fragile X Tremor/Ataxia Syndrome (FXTAS), and females undergo Premature Ovarian Failure (POF1). Here, we have evaluated gene expression profiles from blood in male FMR1 premutation carriers and detected a strong deregulation of genes enriched in FXTAS relevant biological pathways, including inflammation, neuronal homeostasis and viability. Gene expression profiling distinguished between control individuals, carriers with FXTAS and carriers without FXTAS, with levels of expanded FMR1 mRNA being increased in FXTAS patients. In vitro studies in a neuronal cell model indicate that expression levels of expanded FMR1 5'-UTR are relevant in modulating the transcriptome. Thus, perturbations of the transcriptome may be an interplay between the CGG expansion size and FMR1 expression levels. Several deregulated genes (DFFA, BCL2L11, BCL2L1, APP, SOD1, RNF10, HDAC5, KCNC3, ATXN7, ATXN3 and EAP1) were validated in brain samples of a FXTAS mouse model. Downregulation of EAP1, a gene involved in the female reproductive system physiology, was confirmed in female carriers. Decreased levels were detected in female carriers with POF1 compared to those without POF1, suggesting that EAP1 levels contribute to ovarian insufficiency. In summary, gene expression profiling in blood has uncovered mechanisms that may underlie different pathological aspects of the premutation. A better understanding of the transcriptome dynamics in relation with expanded FMR1 mRNA expression levels and CGG expansion size may provide mechanistic insights into the disease process and a more accurate FXTAS diagnosis to the myriad of phenotypes associated with the premutation.
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PMID:Blood expression profiles of fragile X premutation carriers identify candidate genes involved in neurodegenerative and infertility phenotypes. 2441 49

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. 2451 Jun 84

CGG repeat expansion in the FMR1 gene is associated with fragile X syndrome, fragile X-associated tremor/ ataxia syndrome and fragile X-associated primary ovarian insufficiency. In this study, FMR1 gene mutation screening was carried out in 50 patients. Among them, 12 (%24) were POF and 19 (%38) were Fragile-X. We also examined the parents of the Fragile-X patients. DNA was extracted from blood with kit procedure. To examine expansion of the fragile-X CGG repeat, TP-PCR assay was performed and all amplicons were evaluated on an ABI3130XL Genetic Analyzer System by Fragman analysis. The data were analyzed by Gene Mapper Program. As a result of this study, the patients were identified with the fragile-X whose FMR1 gene CGG alleles have been observed in normal range. However, in patients who were referred with premature ovarian failure, pre-mutation frequency was observed as 6.6%. Only limited study in Turkish population reported frequency of pre-mutation carrier in POF and Fragile-X. Detection of pre-mutation carrier is important for next generation to have healthy siblings. We emphasize that TP-PCR technique is clear, reliable, sensitive, easy and fast method to detect pre-mutation. However, full mutations have to be examined by the technique of Southern blot in the diagnosis of fragile-X.
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PMID:FMR1 gene mutation screening by TP-PCR in patients with premature ovarian failure and fragile-X. 2536 35


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