Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fragile X syndrome(FRAXA) is the disease characterized by X-linked mental retardation, large ears, behavioral problems and macroorchidism. FMR-1 gene expression and its function in human organs are not fully understood. We studied the age dependent and tissue specific FMR-1 gene expression using human autopsy materials by means of RT-PCR. Total RNAs were extracted from the tissues and RT-PCR were performed to detect FMR-1 gene expression. Semiquantitative analysis were performed and the amount of FMR-1 gene products were compared with PGK gene products. Significant FMR-1 gene expressions were noted in all tissues tested, however cerebrum, cerebellum and testis demonstrated relatively higher FMR-1 transcripts compared with other organs. Relatively high expressions were noticed in all tissues during fetal/infantile periods. Semiquantitative analysis reveals that FMR-1 gene expressed much stronger especially around the perinatal periods. These results suggested that FMR-1 gene is widely expressed in human tissues and may play an important role during human maturation not only in the central nervous systems but also in other organs including liver and kidney.
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PMID:[Age dependent and tissue specific FMR-1 gene expression in human organs]. 1022 95

The folate sensitive fragile site FRAXE is located in Xq28, 600 kb distal to the fragile X syndrome (FRAXA) fragile site. An unstable GCC triplet repeat responsible for FRAXE exists in the 5' untranslated region of FMR2 gene. Normal alleles range from 10-35 repeats and more frequently 15-20 GCCs. An expanded GCC repeat over 200 is methylated, inactivates FMR2, and results in FRAXE mental retardation. Affected individuals show mild mental retardation and/or autistic symptoms FMR2 is a large gene consisting of 21 exons spanning about 600 kb. FMR2 mRNA is about 9.5 kb and is expressed in the brain(especially in the hippocampus and the amygdala) in adults and also in placenta. The FMR2 protein is 1311 amino acids, contains nuclear localization signals, and is a putative transcription factor.
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PMID:[FRAXE mental retardation]. 1022 96

Fragile X Syndrome (FXS) is an important cause of both mental retardation and neuropsychiatric disorders, producing its effects by a novel genetic mechanism. Complexities of interacting variables: intelligence quotient (IQ), subject age, limitations of neuropsychiatric testing modalities on the one hand, and the complex genetic mechanism on the other, render exact correspondences between genetic, neural, and neuropsychiatric variables problematic. Nevertheless, current research trends show a convergence of genetic, embryologic, neurocognitive, and neurobehavioral studies on an understanding of pathogenesis centered on the protein product of FMR1, FMRP, with a spectrum of neurocognitive and neuropsychiatric dysfunctions and deficits in turn depending upon tissue mosaicism and other factors determining FMRP production in critical tissues. The resulting neurobehavioral phenotype includes deficits in short-term memory, sequential information processing and visual/spatial abilities, pragmatic language abnormalities, dysfunctional social behavior with peers (gaze-avoidance, aloofness), unusual responses to sensory stimuli, and stereotypy. The proposed psychiatric phenotype now includes attention-deficit hpyeractivity disorder (ADHD), avoidant disorder, pervasive developmental disorders, anziety disorders, mood disorders, and schizotypal personality disorder.
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PMID:Neuropsychiatric Aspects of Fragile X Syndrome. 1032 Apr 15

This study presents the first large, population-based molecular investigation of the fragile X (FRAXA) and FRAXE mental retardation syndromes in the Hellenic populations of Greece and Cyprus. The aims of this population screening were to determine the prevalence of FRAXA and FRAXE syndromes among idiopathic mentally retarded (IMR) individuals, to estimate the incidence in the general population, and to investigate the molecular mechanism of instability and expansion of the FMR1-repeat. Ten FRAXA patients were identified to have either the full mutation (eight) or premutation (two) from a Hellenic population of 866 unrelated IMR individuals (611 males and 255 females, age range 3-25 years). No FRAXE patients were identified among the 611 IMR males. The incidence of FRAXA in the Hellenic population of Cyprus is estimated at 1 in 4,246 males. The repeat sites from the FMR1 and FMR2 alleles were accurately determined and showed similar distribution and frequencies with other population studies. The analysis of AGG interspersion within the FMR1-repeat in normal males revealed long, pure CGG repeats within the "gray zone" as well as variation within the 3' end showing polarity of instability. This finding supports the hypothesis that the AGG interspersion and the length of the pure repeat are major factors in determining allele stability. Analysis of FRAXAC1, DXS548, and FRAXAC2 identified particular alleles and haplotypes to have a significant association with either gray zone alleles or alleles >15 pure CGG repeats. We hypothesize that this subgroup of alleles and haplotypes are associated with long pure CGGs (>15 CGG) or 35 repeats and, having shared an evolutionary past, would have the tendency to expand.
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PMID:Molecular screening of fragile X (FRAXA) and FRAXE mental retardation syndromes in the Hellenic population of Greece and Cyprus: incidence, genetic variation, and stability. 1033 87

The fragile X syndrome is the most common inherited form of mental retardation. Haplotype studies using FRAXAC1 and DXS548 polymorphic markers flanking the fragile site have demonstrated linkage disequilibrium at the FMR1 locus. We investigated the association of the FRAXAC1, DXS548 and CGG alleles between normal subjects and mentally retarded (MR) patients of unspecified cause who do have fragile X syndrome. We have evaluated the FRAXAC1 site in 390 normal subjects and 321 MR patients and the DXS548 site in 146 normal and 319 MR subjects. Both FRAXAC1 and DXS548 alleles were determined by application of the polymerase chain reaction. When compared with Caucasians, the normal Chinese population has a different FRAXAC1 allele distribution. There are more AC18 repeat alleles and fewer AC19 repeat alleles. The DXS548 allele distributions were similar between Chinese and Caucasians. The same distribution pattern of FRAXAC1 alleles was found in both normal subjects and MR patients, but there were significant differences in the distribution patterns of DXS548 alleles. The FMR1 CGG-DXS548 and FRAXAC1-DXS548 haplotype distribution between normal subjects and MR patients also differed significantly. Our results suggest a possible association between DXS548 alleles and non-FRAXA mental retardation.
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PMID:FRAXAC1 and DXS548 polymorphisms in the Chinese population. 1295 75

Although fragile X syndrome is caused by the absence of fragile X gene expression, little is known about the pathogenic processes underlying the mental retardation. Recent findings that the fragile X protein, FMRP, contains RNA binding motifs and nuclear transport signals and associates with ribosomes suggest that FMRP may be involved in either mRNA processing, transport, or translation. To test the hypothesis that absence of FMRP may affect the processing of specific transcripts, we have used an RNA differential display assay (RDDA) to identify differentially expressed transcripts in lymphoblast lines derived from fragile X syndrome patients. A 0.9-kb cDNA fragment that showed reduced expression in a fragile X lymphoblast cell line was found to be identical to G3BP (Ras-GTPase-Activating protein SH3-domain-binding protein). Quantitative reverse transcriptase-polymerase chain reaction showed that the expressed levels of G3BP mRNA in fragile X lymphoblast cell lines were significantly less than controls. Our results indicate that G3BP mRNA may be regulated by FMRP and supports the hypothesis that FMRP may modulate the transcription of specific transcripts.
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PMID:Reduced mRNA for G3BP in fragile X cells: evidence of FMR1 gene regulation. 1033 5

Fragile X syndrome is the most common form of inherited mental retardation currently known, associated with a wide range of developmental disabilities in both males and females, caused by a large expansion of a (CGG)n repeat in the first exon of the FMR1 gene. Fragile X syndrome occurs in all racial and ethnic groups, and it is a condition of major epidemiological importance among mentally handicapped males. Therefore, this disease must be considered in the differential diagnosis of any child with developmental delay, mental retardation or learning disability. The fragile X syndrome is due to the shutdown of the FMR1 gene transcription, and the pathogenesis of this syndrome is a consequence of absence of the protein product of the FMR1 gene (FMRP). Since the great majority of fragile X patients have the same type of mutation in a specific location of the gene, molecular analysis is extremely accurate for diagnosis of the disease, and important for genetic counseling of family members. Others genetic disorders are also caused by expanded trinucleotide repeats.
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PMID:Fragile X syndrome (review). 1034 Dec 96

Fragile X syndrome is the most frequent heritable genetic disease involving mental retardation and is usually caused by an expanded CGG repeat in the first exon of the FMR1 gene. Therefore, searching for CGG expansion at the FRAXA locus among the mentally retarded has become a routine investigation in neuro-paediatric practice. Consequently, we have developed a fluorescent PCR-based assay for sizing repeats as an alternative to laborious and time-consuming Southern blot. The procedure utilises a reverse fluorescent labelled primer, and the Expand Long Template PCR system (Roche) with addition of dimethylsulfoxide and 7-deaza-dGTP It allows precise determination of the CGG repeat number in males and females for alleles from normal to premutation size range and detection of full mutations in males. We believe that this PCR protocol, allowing a high sample throughput, is useful for first-line screening among mentally retarded males, possibly complemented by Southern blot analysis to assess the methylation status of large mutated alleles.
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PMID:Improved fluorescent PCR-based assay for sizing CGG repeats at the FRAXA locus. 1036 9

The loss of FMR1 expression due to trinucleotide repeat expansion leads to fragile X syndrome, a cause of mental retardation. The encoded protein, FMRP, is a member of a gene family that also contains the fragile X-related proteins, FXR1P and FXR2P. FMRP has been shown to be a nucleocytoplasmic shuttling protein that selectively binds a subset of mRNAs, forms messenger ribonucleoprotein (mRNP) complexes, and associates with translating ribosomes. Here we describe a cell culture system from which we can isolate epitope-tagged FMRP along with mRNA, including its own message, and at least six other proteins. We identify two of these proteins as FXR1P and FXR2P by using specific antisera and identify a third protein as nucleolin by using mass spectrometry. The presence of nucleolin is confirmed by both reactivity with a specific antiserum as well as reverse coimmunoprecipitation where antinucleolin antiserum immunoprecipitates endogenous FMRP from both cultured cells and mouse brain. The identification of nucleolin, a known component of other mRNPs, adds a new dimension to the analysis of FMRP function, and the approach described should also allow the identification of the remaining unknown proteins of this FMRP-associated mRNP as well as the other bound mRNAs.
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PMID:Isolation of an FMRP-associated messenger ribonucleoprotein particle and identification of nucleolin and the fragile X-related proteins as components of the complex. 1056 18

A total of 106 women affected by premature ovarian failure (POF) were evaluated for fragile X (FRAXA) premutation. The POF patients were classified as having a familial condition (33 women), at least one relative with early menopause (12 women), or a sporadic condition (61 women). The FRAXA premutation was only detected in patients with familial (four out of 33) or sporadic POF (two out of 61). In general, the results obtained indicated that the prevalence [six out of 106, 6%, 95% confidence interval (CI) 3-11%] of FRAXA premutation is significantly higher in women affected by POF than expected (P = 1.24x10(-3)), suggesting a phenotype consequence of the premutation alleles. This relationship is more convincingly derived from the observation in two analysed pedigrees of a co-segregation between FRAXA and POF. These findings suggest a possible involvement of premutated alleles in ovarian failure, and indicate the utility of POF families screening for FRAXA premutation in order to prevent the transmission of mental retardation syndrome.
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PMID:Association between idiopathic premature ovarian failure and fragile X premutation. 1092 Jan 20


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