Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the gene coding for methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT) and have also been reported in a number of X-linked mental retardation syndromes. Furthermore, putative mutations recently have been described in a few autistic patients and a boy with language disorder and schizophrenia. In this study, DNA samples from individuals with schizophrenia and other psychiatric diseases were scanned in order to explore whether the phenotypic spectrum of mutations in the MECP2 gene can extend beyond the traditional diagnoses of RTT in females and severe neonatal encephalopathy in males. The coding regions, adjacent splicing junctions, and highly conserved segments of the 3'-untranslated region (3'-UTR) were examined in 214 patients, including 106 with schizophrenia, 24 with autism, and 84 patients with other psychiatric diseases by detection of virtually all mutations-single strand conformation polymorphism (SSCP) (DOVAM-S). To our knowledge, this is the first analysis of variants in conserved regions of the 3'-UTR of this gene. A total of 5.2 kb per haploid gene was analyzed (1.5 Mb for 214 patients). A higher frequency of missense and 3'-UTR variants was found in autism. One missense and two 3'-UTR variants were found in 24 patients with autism versus one patient with a missense change in 144 ethnically similar individuals without autism (P = 0.009). These mutations suggest that a possible association between MECP2 mutations and autism may warrant further study.
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PMID:MECP2 structural and 3'-UTR variants in schizophrenia, autism and other psychiatric diseases: a possible association with autism. 1521 31

About 80% of female patients with Rett syndrome (RTT) display a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, but most males with MECP2 mutation experience severe fatal encephalopathy or non-specific X-linked mental retardation (XLMR). The existence of male RTT has been extensively discussed. We report herein a boy with classic RTT in a family with a missense mutation in MECP2. The mother exhibited slight mental retardation and was a carrier for R133C. The patient could stand with support at 12-months-old, and stereotypic hand movements appeared at 3-years-old. He became bed-ridden by 8-years-old. The R133C mutation was present in MECP2 without somatic mosaicism. A sister with R133C displayed classic RTT. The R133C mutation has been detected in female patients with classic and preserved speech variant RTT, but not in males with non-specific XLMR. These results suggest that clinical phenotypes caused by DNA mutation in MECP2 are determined by position of the mutation in the gene, and R133 represents a critical amino acid residue in the induction of RTT symptoms in humans.
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PMID:Classic Rett syndrome in a boy with R133C mutation of MECP2. 1612 33

Rett syndrome is a neurodevelopmental disorder that primarily affects girls, most of whom have mutations in the transcription regulatory gene MECP2. However, mutations in MECP2 also have been identified in normal carrier female individuals, female individuals with mild learning disabilities and features of Angelman syndrome, and male individuals with Klinefelter syndrome or Rett syndrome-like features, fatal neonatal encephalopathy, and familial X-linked mental retardation with or without motor abnormalities. Therefore, molecular testing should be considered for a wide spectrum of individuals. As such, Rett syndrome remains a clinical diagnosis. In this article, we also discuss three recent developments: (1) the recognition of significant gallbladder dysfunction, especially in those 20 years of age or younger; (2) a clinical trial of folate and betaine, which produced no objective improvement but did yield a subjective increase in attention and interaction; and (3) measurement of cerebrospinal fluid folate levels in a large cohort, which yielded normal values, indicating no need for supplementation.
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PMID:Rett syndrome: model of neurodevelopmental disorders. 1622 24

Mutations in the methyl-CpG-binding protein 2 (MECP2) gene located on Xq28, cause Rett syndrome (RTT) in female patients. Meanwhile, nonmosaic MECP2 mutations unknown in girls have been found in an increasing number of male patients with a normal 46, XY karyotype. They can cause a broad spectrum of neurodevelopmental disorders which often show a combination of mental retardation (MR) with neurological symptoms. We present the results of MECP2 analysis in a group of 72 male patients with an unexplained combination of MR and neurological features, and review the mutational reports published on male patients since the discovery of the MECP2 gene. Analysis included sequencing of exon 1 which thus far was mostly omitted from DNA screening. One pathogenic mutation has been found in a patient with Rett variant, in addition to an unclassified variant and a series of nonpathogenic changes. No changes have been found in exon 1. Criteria for testing of male patients are classic RTT, severe neonatal encephalopathy, and RTT variant which may be clinically underrecognized. Testing can also be considered in males with a combination of unexplained MR and (progressive) neurological manifestations although the yield of MECP2 analysis is probably low in this situation. Based on the literature, MECP2 testing in males with MR only is debatable.
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PMID:MECP2 mutations are an infrequent cause of mental retardation associated with neurological problems in male patients. 1637 10

Mutations in the MECP2 (Methyl-CpG-binding protein) gene have been reported to cause Rett syndrome (RTT), an X-linked progressive encephalopathy. Recent studies have identified large gene rearrangements that escape the common PCR-based mutation screening strategy and mutations in a novel MeCP2 isoform (named MECP2B). We have collected the results of MECP2 mutational analysis concerning 424 RTT patients conducted in eight laboratories in France. In total, 121 different MECP2 mutations were identified. R168X (11.5%) is the most common of MECP2 mutations, followed by R270X (9%), R255X (8.7%), T158 M (8.3%) and R306C (6.8%). Only eight mutations had relative frequency>3%. Large and complex rearrangements not previously detected using only a PCR-based strategy represent 5.8% of MECP2 mutations. On the contrary, mutation in exon 1 appears to be rare (less than 0.5%). These data demonstrate the high allelic heterogeneity of RTT in France and suggest that routine mutation screening in MECP2 should include quantitative analysis of the MECP2 gene. This study represents an important instrument for molecular diagnosis strategy and genetic counseling in RTT families.
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PMID:Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update. 1647 5

Rett syndrome, a neurodevelopmental disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2), is a leading cause of mental retardation with autistic features in females. MECP2 mutations have also been identified in individuals with a variety of clinical syndromes, including mild learning-disability in females, neonatal encephalopathy in males, and psychiatric disorders, autism and X-linked mental retardation in both males and females. Furthermore, MECP2 duplications have been shown to cause a progressive postnatal neurological disorder. MeCP2 is a transcriptional repressor that binds to methylated CpG dinucleotides flanked by AT-rich segments and recruits a co-repressor complex, thereby altering chromatin structure. Subtle gene expression changes have been identified in Rett patients and mouse models; however, MeCP2 dysfunction has also been shown to cause abnormalities of RNA splicing, suggesting a complex molecular pathogenesis. Discovering which genes are misregulated in the absence of functional MeCP2 and demonstrating their role in causing neuronal dysfunction and disease manifestations are challenging but important steps for understanding the pathogenesis of Rett syndrome and related disorders.
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PMID:MeCP2 dysfunction in Rett syndrome and related disorders. 1664 48

MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.
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PMID:Early progressive encephalopathy in boys and MECP2 mutations. 1683 2

Rett syndrome (RTT) is an X-linked progressive encephalopathy. Mutations in the MECP2 (methyl-CpG-binding protein) gene have been found to cause RTT. In the past few years, the role of MECP2 mutations in patients with mental disorders other than RTT has been studied, finding that mutations in MECP2 also contribute to non-syndromic entities. More recently, it has been demonstrated that RTT shares clinical features with those of Angelman syndrome, another neurodevelopmental disorder. These observations must be confirmed in a large series, to better understand the criteria needed for justifying a molecular test. Consequently, we have searched for MECP2 mutations in 294 patients (43 Angelman and Prader-Willi like included) with mental retardation (MR) of unknown aetiology. We found six polymorphisms (three novel, three previously reported) in 10 patients, one novel unclassified silent change (p.V222V) in a man, and one causative mutation in a girl with MR. Once this case was clinically reviewed, the girl presented symptoms of atypical RTT. The mutation (p.Y141C) lies within the methyl-binding domain, and has only been reported once in another atypical RTT. Our results show that the MECP2 mutations account for a low frequency (1/416 chromosomes = 0.24%) among mentally retarded individuals, which imply that it is necessary to perform an exhaustive clinical examination of patients before determining whether analysis of MECP2 is required or not.
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PMID:Screening for MECP2 mutations in Spanish patients with an unexplained mental retardation. 1687 96

Rett syndrome (RTT) is unique among genetic, chromosomal and other developmental disorders because of its extreme female gender bias, early normal development, and subsequent developmental regression with loss of motor and language skills. RTT is caused by heterozygosity for mutations in the X-linked gene MECP2, which encodes methyl-CpG binding protein 2. MeCP2 is a multifunctional protein that can act as an architectural chromatin-binding protein, a function that is unrelated to its ability to bind methyl-CpG and to attract chromatin modification complexes. Inactivating mutations that cause RTT in females are not prenatally lethal in males, but lead to profound congenital encephalopathy. Molecular diagnoses of RTT, through demonstration of a MECP2 mutation, made at an early stage of the disorder, usually confirm the sporadic nature and very low recurrence risk of the condition. A positive DNA test result, however, also predicts the inevitable clinical course, given the lack of effective intervention. Initial hypotheses indicating that the MeCP2 protein acts as a genome-wide transcriptional repressor were not confirmed by global gene expression studies in various tissues of individuals with RTT and mouse models of MeCP2 deficiency. Rather, recent evidence points to low-magnitude effects of a small number of genes--including the brain--derived neurotrophic factor pathway and glucocorticoid response genes-that might affect formation and maturation of synapses or synaptic function in postmitotic neurons.
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PMID:Mechanisms of disease: neurogenetics of MeCP2 deficiency. 1693 52

We report on three patients with MeCP2 mutation and male Rett phenotypes. Two brothers with T158M mutations and normal karyotype had a severe early onset encephalopathy, progressive microcephaly, severe feeding problems, breathing and sleep disturbances. They died at the ages of 1 year and 8 months, and 3 years and 1 month. This mutation has previously been reported in three males. The phenotypes show a strong resemblance, and might in fact represent a clinical-genetic entity of the T158M mutation within the complex of congenital encephalopathies in males with MeCP2 mutations. We also report a 3-year-old boy with a R294X mutation, normal karyotype, and a more protracted course. He was inactive and sucked poorly from start. The head growth decelerated from the age of 6 months and the feeding problems increased requiring gastrostomy. He had a rapid deterioration period at 2 years and lost sitting and hand grasping functions. He had prolonged periods with tremor and epileptic myoclonus, shifting tonus, and dystonic extension of the trunk and legs, bruxism, and irregular breathing. He was clinically stable with preserved visual and emotional contact function by the age of four years. None of the boys had dysmorphic features.
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PMID:Male Rett phenotypes in T158M and R294X MeCP2-mutations. 1723 9


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