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)

Rett syndrome (RTT), the second most common cause of mental retardation in females, has been associated with mutations in MeCP2, the archetypical member of the methyl-CpG binding domain (MBD) family of proteins. MeCP2 additionally possesses a transcriptional repression domain (TRD). We have compared the gene expression profiles of RTT- and normal female-derived lymphoblastoid cells by using cDNA microarrays. Clustering analysis allowed the classification of RTT patients according to the localization of the MeCP2 mutation (MBD or TRD) and those with clinically diagnosed RTT but without detectable MeCP2 mutations. Numerous genes were observed to be overexpressed in RTT patients compared with control samples, including excellent candidate genes for neurodevelopmental disease. Chromatin immunoprecipitation analysis confirmed that binding of MeCP2 to corresponding promoter CpG islands was lost in RTT-derived cells harboring a mutation in the region of the MECP2 gene encoding the MBD. Bisulfite genomic sequencing demonstrated that the majority of MeCP2 binding occurred in DNA sequences with methylation-associated silencing. Most importantly, the finding that these genes are also methylated and bound by MeCP2 in neuron-related cells suggests a role in this neurodevelopmental disease. Our results provide new data of the underlying mechanisms of RTT and unveil novel targets of MeCP2-mediated gene repression.
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PMID:The impact of MECP2 mutations in the expression patterns of Rett syndrome patients. 1554 94

Mutations in the methyl-CpG-binding protein 2 (MECP2) gene are known to underlie Rett' syndrome, the most common cause of mental retardation (MR) in girls. Since the original report, phenotypes resulting from MECP2 mutations have been shown to extend, for example, to several Rett variants, autism, atypical Angelman syndrome, and nonspecific MR. It was earlier proposed that MECP2 mutations might account for approximately 2% of the male cases with nonspecific MR. Thereby, the frequency of MECP2 mutations in the mentally retarded population would be comparable to that of Fragile-X syndrome. The aim of this study was to analyze well-characterized cases with MR and to clarify the role of the MECP2 gene in the etiology of MR and atypical Angelman syndrome. The coding sequence of the MECP2 gene was analyzed in a sample of 118 patients (103 males, 15 females) by direct sequencing. Two coding sequence variants, 602C > T (A201V) and 1189G > A (E397K), were identified. In addition, we identified four variants in the intronic or 3'UTR regions. None of these variants is likely to be causal. We conclude that the evidence across all the mutation screening studies implies that MECP2 mutations do not represent a major cause of nonspecific MR.
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PMID:MECP2 mutation analysis in patients with mental retardation. 1557 81

Rett syndrome (RS), a neurological developmental disorder, is one of the commonest causes of cognitive impairment in girls and women. These patients are often initially misdiagnosed as idiopathic mental retardation, cerebral palsy, or autism. Despite several reports from the West, there are very few reports from the Indian population. We present four female children with RS and emphasize the importance of early diagnosis.
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PMID:Recent experience with Rett syndrome at a tertiary care center. 1562 43

Autonomic nervous system involvement in female patients with classic Rett syndrome usually manifests as breathing abnormalities, peripheral vasomotor disturbances, and cardiac sympathetic imbalance, the latter a possible cause of sudden death. MECP2 gene mutations responsible for Rett syndrome have also been found in male patients with mental retardation, sometimes associated with different neurologic abnormalities. However, autonomic nervous system functions have never been investigated in male patients with X-linked mental retardation owing to MECP2 mutations. We studied heart rate variability, a marker of autonomic activity, in a family with the MECP2 mutation in male patients, one of whom had died suddenly. Cardiovascular features similar to those observed in a Rett syndrome variant with preserved speech were found, suggesting sympathetic imbalance.
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PMID:Autonomic dysfunction in mental retardation and spastic paraparesis with MECP2 mutation. 1570 71

In mammals, methyl-CpG binding proteins play a significant role in the control of gene expression through their association with chromatin-remodeling complexes. Mutations in the gene coding for methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome and have also been reported in a number of X-linked mental retardation diseases. In this study, DNA samples from 363 male individuals with syndromic and non-syndromic mental retardation and other psychiatric diseases were screened for A140V (419C>T) mutation in the MECP2 gene, considered the most frequent MECP2 mutation in males. No 419C>T was found suggesting that the A140V mutation in the MECP2 gene is not a common cause of mental retardation in males. Recently, a new and abundant isoform of MECP2 was described, which has an alternative N-terminus, translated from exon 1, that was previously thought to be non-coding and has been excluded from many mutational screening, as well, the 5' and 3' UTR regions. We consider essential proceeding further screening in the whole extension of the MECP2 gene using clinically well-documented and larger sized sample to assure the overall contribution of MECP2 to mental retardation.
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PMID:The A140V mutation in the MECP2 gene is not a common etiological factor among Brazilian mentally retarded males. 1581 90

Rubinstein-Taybi syndrome (RTS; MIM# 180849) is a well-known malformation syndrome, characterized by broad thumbs and halluces, a characteristic facies, short stature, and mental retardation. RTS is accompanied by a variety of morbid complications, particularly of the skeleton. Based on the experience of five RTS patients with malformation of the craniovertebral junction, we draw attention to previously unrecognized life-threatening complications of RTS, including instability of C1-C2, os odontoideum, hypoplasia of the dens, and fusion of the cervical vertebrae. One patient developed severe cervical myelopathy. Malformation of the cervical spine may be a common syndromic constituent of RTS, to which special attention should be paid to prevent its neurologic sequelae.
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PMID:Congenital anomaly of cervical vertebrae is a major complication of Rubinstein-Taybi syndrome. 1583 59

Mental retardation has been categorized into severe mental retardation where genetics plays a very important role and mild mental retardation, in which genetics in some instances plays a role but in which cultural factors also matter a great deal. The pathogenetic, clinical and behavioral characteristics of genetically determined disorders associated with mental retardation differ greatly-as exemplified by two genetic disorders that have been clarified recently, namely Rett syndrome and the Williams syndrome. In the work-up of the developmentally disabled child, previous studies have shown that genetic studies are of have great importance and high yield. Early biochemical diagnosis in newborn screening has tremendous potential and has been strongly supported by NICHD-the PKU story being so much part of what NICHD has done. We must gain a better understanding of structure/function relationships, which becomes more and more possible with neuroimaging. A better understanding of neural plasticity can lead to correction by early intervention.
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PMID:Genetic causes of mental retardation. 1583 96

Classical methyl-CpG binding proteins contain the conserved DNA binding motif methyl-cytosine binding domain (MBD), which preferentially binds to methylated CpG dinucleotides. These proteins serve as transcriptional repressors, mediating gene silencing via DNA cytosine methylation. Mutations in methyl-CpG binding protein 2 (MeCP2) have been linked to the human mental retardation disorder Rett syndrome, suggesting an important role for methyl-CpG binding proteins in brain development and function. This mini-review summarizes the recent advances in studying the diverse functions of MeCP2 as a prototype for other methyl-CpG binding proteins in the development and function of the vertebrate nervous system.
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PMID:Methyl-CpG binding proteins in the nervous system. 1585 80

Methyl-CpG binding protein 2 gene (MECP2), the gene implicated in Rett syndrome, was also reported to be involved in mental retardation and autism. MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a nuclear protein family sharing the methyl-CpG binding domain (MBD) and are related to transcriptional repression. In 65 Japanese autistic patients, all the exons of each gene were screened for mutations by DHPLC, and the results were confirmed by direct sequencing. An R269C mutation that resulted in the addition of cysteine near a cysteine rich region was found in the MBD1 gene in one patient. This mutation was also detected in the patient's father with some phenotypes of autism and his normal sister, but not in 151 controls. Two repeat length polymorphisms, (GGGGCC)2 to 3 and (GGC)4 to 5, were detected in MBD2, and several polymorphisms were detected in each gene. Although our findings could not confirm that the genes of this family are responsible for the etiology in the majority of autistic patients, the R269C mutation in the MBD1 gene may relate to autism. The potential association of the high-polymorphic gene variants with autism needs to be studied further. Furthermore, these polymorphisms are useful for linkage analysis.
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PMID:Mutation analysis of methyl-CpG binding protein family genes in autistic patients. 1596 18

We detected morphologic abnormalities in the cerebral cortex of Mecp2-hemizygous (Mecp2(-/y)) mice. The cortical thickness of both somatosensory and motor cortices in mutants did not increase after 4 weeks of age, as compared with that in wild-type male mice. The density of neurons in those areas was significantly higher in layers II/III and V of Mecp2(-/y) mice than in wild-type mice, particularly in layers II/ III after 4 weeks of age. In layer II/III of the somatosensory cortex of Mecp2(-/y) mice, the diameter of the apical dendrite was thin and the number of dendritic spines was small. Electron microscopy revealed that two-week-old mutants already had numerous premature postsynaptic densities. These results indicate that Mecp2(-/y) mice suffered delayed neuronal maturation of the cerebral cortex and that the initial neuronal changes were caused by premature synaptogenesis. Rett syndrome patients with a heterozygous mutation of Mecp2 display developmental disorders including cortical malfunctions such as mental retardation, autism, and epilepsy. Our results provide evidence of the similarity with Rett syndrome brains in some respects and suggest that MeCP2/Mecp2 plays some role in synaptogenesis.
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PMID:Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. 1597 46


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