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)

The fragile X syndrome is the most frequent form of inherited mental retardation. This is caused by the transcriptional inactivation of the FMR1 gene. The KH domain is an evolutionarily conserved sequence motif present in many RNA-binding proteins including the fragile X mental retardation gene product. We have studied the expression of the gene in fresh leukocytes derived from patients and normal controls by using a reverse transcriptase-polymerase chain reaction (RT-PCR) protocol that amplifies the region of the FMR1 that contains the KH1 and KH2 domains and that has not been used in previous studies. As expected, normal expression was observed in control subjects and carriers, but FMR1 mRNA was absent in male patients with fragile X syndrome. This method was also proved to be useful for testing the expression of FMR1 in samples from several species and tissues. In all cases we obtained a similar and unique transcript. We suggest that RT-PCR from the KH domains could be the method of choice for studying FMR1 expression.
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PMID:Assessment of FMR1 expression by reverse transcriptase-polymerase chain reaction of KH domains. 948 1

Mental retardation due to fragile X syndrome is one of the genetic disorders caused by triplet repeat expansion. CGG repeat involved in this disease is known to exhibit polymorphism even among normal individuals. Here we describe the development of suitable probes for detection of polymorphism in CGG repeat at FMR1 locus as well as the diagnosis of fragile X syndrome. Using these methods polymorphism at the FMR1 locus has been examined in 161 individuals. Ninety eight patients with unclassified mental retardation were examined, of whom 7 were found to have the expanded (CGG) allele at the FMR1 locus. The hybridization pattern for two patients has been presented as representative data.
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PMID:Triplet repeat polymorphism & fragile X syndrome in the Indian context. 952 78

The fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by an expansion of a polymorphic CGG repeat upstream of the coding region in the FMR1 gene. The expansion blocks expression of the FMR1 gene due to methylation of the FMR1 promoter. Functional studies on the FMR1 protein have shown that the protein can bind RNA and might be involved in transport of RNAs from the nucleus to the cytoplasm. A role of FMR1 protein on translation of certain mRNAs has been suggested. An animal model for fragile X syndrome exists and these mice show some behavioural difficulties mimicking the human fragile X syndrome phenotype. This review presents what is known about the protein and what is learned from the animal model for fragile X syndrome.
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PMID:Animal model for fragile X syndrome. 956 25

We examined the prevalence of the fragile X mental retardation (FMR1) full mutation and fragile X E mutation (FMR2) among preschoolers evaluated for language delay. A total of 534 preschoolers recruited from a Developmental Pediatric or Speech and Language Disorders clinic were tested with Southern blot and polymerase chain reaction DNA analyses; 3 were found to have the FMR1 full mutation. None of the 534 children tested positive for the FMR2 full mutation; however, 3 children had unusually small FMR2 alleles suggestive of FMR2 deletions. Screening for fragile X among language-delayed preschoolers is warranted, particularly when there is a family history of mental retardation, but regardless of sex or the presence of behavioral or physical features associated with the fragile X phenotype. The potential benefit of screening for FMR2 alterations is an unexpected implication of the study and is worthy of continued exploration.
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PMID:The prevalence of the FMR1 and FMR2 mutations among preschool children with language delay. 960 81

Fragile X syndrome is the most common from of inherited mental retardation. Approximately half of females with the full mutation have significant cognitive deficits, whereas females with the premutation do not. Phenotypic effects seen in 281 females (IQs from 64 to 139) were analyzed. Results showed that females with the full mutation differ significantly from controls on selected anthropometric measurements, physical index score, and various behavioral features. Females with the premutation differed significantly from controls in regards to a few anthropometric measurements and the physical index score but not in behavioral features. These results suggest that phenotypic effects of the FMR1 mutation are not only common in females with the full mutation, but in females with the premutation as well.
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PMID:Phenotypic involvement in females with the FMR1 gene mutation. 960 68

X inactivation is the process by which mammalian females achieve dosage compensation by transcriptionally silencing one X chromosome. In chromosomally normal females, this process is random. However, most females with one abnormal X chromosome demonstrate complete skewing of X inactivation, presumably as the result of cell selection. We present a mentally retarded girl with a 46,X,t(X;9)(q28;q12) karyotype. Analysis of this patient's lymphocytes, using late replication banding and methylation assays for the androgen receptor (AR) and fragile X mental retardation (FMR1) genes, did not show the predicted nonrandom X inactivation pattern. Thus, this patient is functionally disomic for Xq28-qter in a proportion of her cells, most likely resulting in her abnormal phenotype. This case demonstrates the utility of correlating X inactivation patterns with phenotype in females with one structurally abnormal X chromosome, and suggests that both cytogenetic and molecular X inactivation studies should be included in the routine study of these individuals.
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PMID:Random X inactivation in a girl with a balanced t(X;9) and an abnormal phenotype. 963 70

The fragile X syndrome is characterised by mental retardation, behavioural features, and physical features, such as a long face with large protruding ears and macro-orchidism. In 1991, after identification of the fragile X mental retardation (FMR1) gene, the cytogenetic marker (a fragile site at Xq27.3) became replaced by molecular diagnosis. The fragile X syndrome was one of the first examples of a "novel" class of disorders caused by a trinucleotide repeat expansion. In the normal population, the CGG repeat varies from six to 54 units. Affected subjects have expanded CGG repeats (>200) in the first exon of the FMR1 gene (the full mutation). Phenotypically normal carriers of the fragile X syndrome have a repeat in the 43 to 200 range (the premutation). The cloning of the FMR1 gene led to the characterisation of its protein product FMRP, encouraged further clinical studies, and opened up the possibility of more accurate family studies and fragile X screening programmes.
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PMID:The fragile X syndrome. 1005 Oct 22

We determined the CGG repeat length and AGG interruptions in the FMR1 gene in normal Chinese subjects and patients with infantile autism and mild mental retardation. Genomic DNA was investigated by PCR and Southern hybridisation for CGG repeat number and PCR with Mnl I restriction analysis for AGG interruption. Both the normal subjects and the patients with autism have 53 CGG repeats in FMR1, and the majority have two interspersed AGG. Our normal Chinese subjects have a similar number of interspersed AGG as other populations. When compared with the normal subjects, the autism patients have less AGG interruptions and a different pattern of AGG distribution. There was a significant difference in the CGG configurations between normal subjects and patients with autism. The latter had less interspersed AGG, as in fragile X patients, but they did not have fragile X. A study on mentally retarded patients with no infantile autism should also be carried out to ascertain whether mental retardation alone may have contributed to such AGG pattern.
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PMID:CGG repeat interruptions in the FMR1 gene in patients with infantile autism. 980 79

The fragile X syndrome is characterized by X-linked mental retardation with additional features such as a long face with large protruding ears, macroorchidism, and eye-gaze avoidance. The disorder is caused by an abnormally expanded CGG repeat within the first exon of the fragile X mental retardation (FMR1) gene that is associated with shutdown of transcription and absence of the fragile X mental retardation protein (FMRP). Detection of patients and carriers of the fragile X syndrome is done by DNA analysis of the CGG repeat, whereas the FMRP antibody test allows rapid detection of male patients using bloodsmears. In a screening program for the fragile X syndrome in the southwest of the Netherlands, 412 males with mental retardation of unknown cause were subjected to the protein test. The patients were scored for fragile X features and their DNA tested for the FMR1 mutation, as reported previously. The FMRP test detected two fragile X patients with a repeat expansion in FMR1, whereas normal protein expression was observed in all the retarded male patients with a normal repeat. The FMRP test was found to be suitable for screening among a large population of retarded males. The results also suggest that mutations other than the CGG repeat leading to absence of detectable FMRP are apparently rare among mentally retarded males.
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PMID:Screening with the FMR1 protein test among mentally retarded males. 985

A family with X linked inheritance of mental retardation (XLMR) is presented. There are 10 mentally retarded males and two affected females in two generations. There are four obligatory carriers, one of whom is described as "slow". Most affected males show macrocephaly and macro-orchidism, which are typical signs of the fragile X syndrome, but have been tested cytogenetically and by analysis of the FMR1 gene and do not have this syndrome. However, some normal males in the family also exhibit macro-orchidism and macrocephaly. Linkage analysis using markers derived from the X chromosome indicates that the causative gene in this family is located in the proximal long arm of the X chromosome, in the interval Xp11-q21. Maximum lod scores of 2.96 with no recombination were found at three loci in Xq13-q21: DXS1111, DXS566, and DXS986. Recombination was observed with DXS1002 (Xq21.31) and DXS991 (Xp11.2), loci separated by about 30 Mb. Although isolation of the gene in this family will be difficult because of the size of the region involved, the localisation should be helpful in investigating other similar families with XLMR, macrocephaly, and macro-orchidism not attributable to FMR1.
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PMID:A family with mental retardation, variable macrocephaly and macro-orchidism, and linkage to Xq12-q21. 986 1


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