Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FMR2 is the gene associated with FRAXE mental retardation. It is expressed as an 8.7-kb transcript in placenta and adult brain. A fetal-specific FMR2 transcript of approximately 12 kb was detected in fetal brain and at a lower level in fetal lung and kidney. FMR2 is a large gene composed of 22 exons spanning at least 500 kb on Xq28. Alternative splicing involving exons 2, 3, 5, 7, and 21 was not tissue specific as tested on mRNA from human fetal and infant brain. FMR2 is translated into a 1311-amino-acid nuclear protein with putative transcription transactivation potential. Subcellular localization studies with green fluorescent protein as a reporter show that both nuclear addresses found in the FMR2 sequence are functional and direct the FMR2 protein into the nucleus. FMR2 together with AF4 and LAF4 forms a new family of nuclear proteins with DNA-binding capacity and transcription transactivation potential. BLAST searches of the dbEST database revealed the presence of at least two other groups of nonoverlapping ESTs showing high similarity to the FMR2-related family of proteins. One of them, represented by the EST W26686, maps to chromosome 5q31. Amino acid similarity among the proteins encoded by members of the gene family is high in the NH2 terminus, low in the middle, and high again in the COOH end. Available information from members of the family shows that genomic organization is conserved. This FMR2-related gene family encodes nuclear proteins with involvement in mental retardation (FMR2), cancer (AF4), and lymphocyte differentiation (LAF4) or with unknown function (EST W26686 and/or AA025630).
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PMID:Gene structure and subcellular localization of FMR2, a member of a new family of putative transcription activators. 929 37

Fragile X syndrome is the most common inherited form of familial mental retardation. It results from a (CGG)n trinucleotide expansion in the FMR1 gene leading to the typical Martin-Bell phenotype. Clinical features vary depending on age and sex. Expansion of a (CCG)n repeat in the FMR2 gene corresponds to the FRAXE fragile site which lies distal to FRAXA and is also associated with mental retardation, but it is less frequent and lacks a consistent phenotype. Analysis of repeat expansions in these two genes allows the molecular diagnosis of these different entities. We report here the screening of the FRAXA and FRAXE mutations in 222 unrelated mentally retarded individuals attending Spanish special schools. PCR and/or Southern blotting methods were used. We detected full mutations in the FMR1 gene in 11 boys (4.9%) and 1 boy (0.5%) with a CCG repeat expansion in the FMR2 gene. The latter shows mild mental retardation with psychotic behaviour and no remarkable physical traits. Molecular studies revealed a mosaicism for methylation in the FMR2 gene. This case supports the observation that expansions greater than 100 repeats can be partially methylated and cause the phenotype.
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PMID:Screening for FMR1 and FMR2 mutations in 222 individuals from Spanish special schools: identification of a case of FRAXE-associated mental retardation. 934 61

The FRAXE fragile site, 600 Kb distal to the more common FRAXA, has been reported to be expressed in subjects with mild nonsyndromal mental retardation. Amplification of more than 200 GCC repeats associated with methylation of the adjacent CpG island at Xq28 is responsible for FRAXE fragility. We describe two unrelated, mentally retarded males identified during a screening for fragile X syndrome. Both index cases underwent FRAXE molecular analysis, following cytogenetic expression of the fra X site and negative FRAXA test. In family 1, we were able to investigate other 13 subjects over three generations, identifying two additional FRAXE-positive males, one with a fully mutated allele and one with a mosaic genotype. Detailed evaluation of physical traits and psychometric tests was performed on three retarded males from family 1 and the propositus from family 2. All of them were found to lack a definite phenotype, and showed different degrees of mental retardation. Slight mental retardation was evident in the mosaic male, suggesting that methylation might be an important determinant of mental impairment.
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PMID:Molecular characterization of FRAXE-positive subjects with mental impairement in two unrelated Italian families. 947 3

Mutations at FRAXA and FRAXE loci are due to expansions of a CGG trinucleotide repeat and are characterized by mental retardation. Here we report a pilot screening survey by means of cytogenetic and molecular methods of 433 unrelated retarded individuals and their parents of Hellenic origin coming from various parts of Greece and Cyprus. The purpose of the study was to estimate the frequency of FRAXA mutation in individuals with nonspecific mental retardation without family history and phenotypic stigmata in the Hellenic population. Five FRAXA-positive children (1.15%) were identified, of whom four were found to carry a full mutation and one a premutation. Furthermore we present preliminary data on a screening of FRAXE mutation frequency. We screened 257 male patients with nonspecific mental retardation, finding none positive for FRAXE mutation.
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PMID:FRAXA and FRAXE prevalence in patients with nonspecific mental retardation in the Hellenic population. 952 14

Fragile X (FraX) syndrome is the most common cause of inherited mental retardation. To see whether FRAXA or FRAXE can account for the etiology of some unexplained neurodevelopmental disorders in children, we screened for trinucleotide repeat expansion in a consecutive cohort of 73 Chinese children and their mothers seen in 1995 (group 1) referred for developmental assessment due to developmental delay, language delay, attention deficit hyperactivity disorder, autistic spectrum disorder, mental retardation and/or learning disability. We also screened DNA samples of all five previously diagnosed cytogenetically-positive FraX boys, their mothers and sisters (group 2). A control group of unrelated teenagers and adults were recruited from the community (group 3). In group 1, 3 families (2 mothers and a mother and her son) were found to carry a small premutation allele at FRAXA (premutation frequency = 2%, 3/153 independent X chromosomes), but none had any expansion at FRAXE. In group 2, all 5 FraX boys had full mutation at FRAXA and normal repeat length at FRAXE. In group 3, 1 male has a premutation allele out of 18 males and 59 females tested (premutation frequency of control = 0.7%, 1 out of 136 X chromosomes). For FRAXE screening in group 3, 2 females were carriers (1.5%, 2 out of 136 X chromosomes). Thus, FRAXA and FRAXE cannot account for the etiology of neurodevelopmental disorders in our cohort of Chinese children, and the prevalence of FRAXE mutation in normal Chinese population appears to be higher than reported in the Caucasians.
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PMID:DNA diagnosis of FRAXA and FRAXE in Chinese children with neurodevelopmental disorders and fragile X syndrome. 963 71

FRAXA, FRAXE, and FRAXF are folate-sensitive fragile sites originally discovered in patients with X-linked mental retardation. The FMR1 gene, whose first exon includes the FRAXA site on Xq27.3, accounts for 15-20% of all X-linked forms of mental retardation. Loss of expression of FMR2, a gene adjacent to the FRAXE site on Xq28, is correlated with FRAXE expansion in some mild mentally retarded patients. FRAXF is a fragile site whose expression has not been associated with any pathological phenotype. The fragility in all three sites is caused by expansions of CGG repeats adjacent to hypermethylated CpG islands. The prevalence of FRAXA, FRAXE, and FRAXF remains uncertain because of the lack of a simple and cost-effective test allowing wide screening programs. For the same reason, the real phenotype-genotype correlations in FRAXE and FRAXF are uncertain as well. We have developed a rapid multiplex polymerase chain reaction (PCR) assay in which hypermethylated CpG islands adjacent to FRAXA, FRAXE, and FRAXF are displayed. The test is very simple and cost-effective, requires only 30 microl of peripheral blood, and can be used for performing diagnoses, postnatal and prenatal, and for screening large groups of control and mentally retarded males and newborn boys.
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PMID:A simple multiplex FRAXA, FRAXE, and FRAXF PCR assay convenient for wide screening programs. 1009 54

FMR2 is the gene associated with FRAXE fragile site non-specific mental retardation (FRAXE MRX). Previously a male patient was identified with developmental delay and speech problems who had a deletion within intron 3 of FMR2. No known FMR2 exonic sequences were missing in this patient. Detailed northern blot analysis revealed existence of a new large isoform of FRM2 in foetal brain. This isoform was characterised and found to be due entirely to an addition of an extra 4.9 kb of the 3' UTR to the previously characterised 8.755 kb FMR2 transcript. This excluded involvement of the large FMR2 isoform in the MRX phenotype of three individuals now known to have the same deletion of intron 3 FMR2 sequences. Expression studies on the new 13.7 kb FMR2 isoform show that it is expressed predominantly in foetal brain and adult pituitary gland, whilst the expression of the shorter previously characterised 8.755 kb isoform is broader, including testis, thymus and placenta. Possible consequences of the alternative processing and expression of FMR2 for the molecular pathology of FRAXE MRX are discussed.
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PMID:Characterisation and expression of a large, 13.7 kb FMR2 isoform. 1019 98

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

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 transcriptional silencing of the FMR2 gene has been implicated in FRAXE mental retardation. FRAXE individuals have been shown to exhibit learning deficits, including speech delay, reading and writing problems. FMR2 encodes a large protein of 1311 amino acids and is a member of a gene family encoding proline-serine-rich proteins that have properties of nuclear transcription factors. To characterize the expression of the fragile X mental retardation 2 (FMR2) protein, polyclonal antibodies were raised against two regions of the human FMR2 protein and used in immunofluorescence experiments on mouse brain cryosections. Our results demonstrate for the first time that the FMR2 protein is localized in neurons of the neocortex, Purkinje cells of the cerebellum and the granule cell layer of the hippocampus. FMR2 staining is shown to colocalize with the nuclear stain 4,6-diamidino-2-phenylindole (DAPI) confirming that FMR2 is a nuclear protein. The localization of FMR2 protein to the mammalian hippocampus and other brain structures involved with cognitive function is consistent with the learning deficits seen in FRAXE individuals.
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PMID:Localization of the fragile X mental retardation 2 (FMR2) protein in mammalian brain. 1065 94


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