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MECP2 Gene (mecp2 + gene)
Selected AbstractsMutations and polymorphisms in the human methyl CpG-binding protein MECP2,,HUMAN MUTATION, Issue 2 2003Gabriel Miltenberger-Miltenyi Abstract Rett syndrome (RTT or RS) is a neurodevelopmental disorder and one of the most frequent genetic diseases in girls. Mutations of the MECP2 gene have been found in a variety of different RTT phenotypes. The MECP2 gene (Xq28) has been described in 1992. Up to now, 218 different mutations have been reported in a total group, of more than 2,100 patients. Mutations in the MECP2 gene are responsible for up to 75% of the classical RTT cases. The mutations, are distributed along the whole gene and are comprised of all types of mutations. Several polymorphisms and benign genetic variants have also been described. Apart from spared reported familial cases, almost all cases are sporadic. RTT syndrome has been considered to be a lethal trait in males. Studying the parental origin of the mutations, however, we and others have found a very high prevalence of de novo mutations on the paternal chromosome. In this work we summarize the mutational reports published until now. One of our aims was to check the mutations' descriptions for consistency and particularly to rename them according to the recommended mutation nomenclature. The increasing number of investigations on the functions of the MeCP2 can help to gain more information about the neuropathogenetic mechanisms causing RTT. Hum Mutat 22:107,115, 2003. © 2003 Wiley-Liss, Inc. [source] Five novel frameshift mutations in exon 3 and 4 of the MECP2 gene identified in Rett patients: Consequences for the molecular diagnosis strategyHUMAN MUTATION, Issue 3 2001Thierry Bienvenu Abstract Rett syndrome (RTT) is a severe progressive neurological disorder that affects almost exclusively females. The gene responsible for this disorder, MECP2, was recently identified by candidate gene strategy. Mutations were detected in 70-85% of RTT cases. We report here five novel frameshift mutations (named 345delC, 895del202, 989ins18del8, 996insAG and 1124del53) in exon 3 and 4 of the MECP2 gene. To avoid the missing of few small deletions in RTT patients using classical mutation screening approaches, we suggest that screening of the mutations in the MECP2 gene in RTT girls should include at least a large PCR to amplify exon 4 entirely. Hum Mutat 18:251,252, 2001. © 2001 Wiley-Liss, Inc. [source] Aminoglycoside-mediated partial suppression of MECP2 nonsense mutations responsible for Rett syndrome in vitroJOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2010Andreea C. Popescu Abstract Rett syndrome is a pediatric neurological condition that affects primarily girls. Approximately 30% of Rett syndrome cases arise from point mutations that introduce a premature stop codon into the MECP2 gene. Several studies have now shown that certain aminoglycosides can facilitate read-through of some types of nonsense mutations in a context-dependent manner and allow the generation of a full-length protein. It remains mostly unclear whether different nonsense mutations of MECP2 will be responsive to aminoglycoside treatment. In this study, we tested whether the common premature terminating mutations of MECP2 seen in Rett syndrome cases can be partially suppressed by aminoglycoside administration. Our results show that aminoglycosides allow different mutant forms of MECP2 to be overcome in transiently transfected HEK293 cells, but with differing levels of efficiency. In addition, we also show that aminoglycosides increased the prevalence of full-length MeCP2 protein in a dose-dependent manner in a lymphocyte cell line derived from a Rett syndrome girl with the R255X mutation. This study helps to establish the "proof of principle" that some nonsense mutations causing Rett syndrome can be at least partially suppressed by drug treatment. © 2010 Wiley-Liss, Inc. [source] Trisomy 21 and Rett syndrome: A double burdenJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 7 2004H Leonard Abstract: Rett syndrome is a severe neurodevelopmental disorder generally affecting girls. Affected individuals are apparently normal at birth but later pass through a period of regression with loss of hand and communication skills and the development of hand stereotypies and dyspraxia. Mutations in the methyl-CpG binding protein 2 (MECP2) gene, have now been found to cause Rett syndrome in up to 80% of classical cases. We report a girl with Down syndrome, one of three children with birth defects in a family of five. From the age of 18 months she developed symptomatology considered by her primary physician to be very characteristic of Rett syndrome. However, this remained a clinical diagnosis till the age of 12 years. Laboratory confirmation of the dual diagnosis, which includes a R168X mutation in the MECP2 gene in addition to trisomy 21, has now been possible. The presence of one neurological or developmental disorder does not necessarily preclude a diagnosis of Rett syndrome. [source] Family data in Rett syndrome: Association with other genetic disordersJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 4 2000H Leonard Background: Rett syndrome is a neurological disorder, almost exclusively affecting girls. Methodology: Between 1993 and 1995 pedigree data were obtained from families of girls registered with the Australian Rett syndrome database. Results: Although 21 individual disorders were reported to be present in family members of affected girls, there was no apparent clustering of the same disorder in different families. However it was certain that a geneticist had been involved in only 10.9% of cases. Conclusions: Mutations in the MECP2 gene have now been reported in a proportion of sporadic cases. Thus, it will be important to examine this phenotype,genotype correlation in the Australian cohort. Where a mutation is found, prenatal diagnosis in a subsequent pregnancy will be a possibility. Using the Australian population database and in conjunction with the clinical genetic services in each state it is planned to contact families with an affected girl to offer testing and counselling. [source] Abnormal movements in Rett syndrome are present before the regression period: A case studyMOVEMENT DISORDERS, Issue 15 2007Teresa Temudo MD Abstract The suspicion of a diagnosis of Rett syndrome (RTT) is based on clinical criteria that are often not present in the first two stages of the disease, as many of its symptoms will appear at a later age. This sometimes postpones the genetic diagnosis and an early clinical intervention. We present the case of 19-months-old girl who came to the consultation because of an arrest of psychomotor development noticed 5 months earlier without change in sleep pattern, behavior, or social communication. In the observation of 1 hour videotape, she presented subtle stereotypic movements of the face and hands as well as repetitive dystonic posturing of her limbs. A genetic test confirmed the diagnosis of RTT, showing a truncating mutation in the MECP2 gene (R270X). This case confirms that stereotypic movement anomalies, albeit infrequent and subtle, are already present before the regression stage and while maintaining prehension and that, in addition, repetitive dystonic postures may occur. Recognition of these early movement disorders will improve clinicians' ability to perform an earlier diagnosis of RTT. © 2007 Movement Disorder Society [source] The Rett Syndrome Behaviour Questionnaire (RSBQ): refining the behavioural phenotype of Rett syndromeTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 8 2002Rebecca H. Mount Background: Although physical features, including loss of hand skills, deceleration of head growth, spasticity and scoliosis, are cardinal features of Rett syndrome (RS), a number of behavioural features are also associated with the disorder, including hand stereotypies, hyperventilation and breath holding. No study has tested the specificity of these behavioural features to individuals with RS, compared to individuals with severe to profound mental retardation (SMR). Method: A novel checklist of characteristic RS behavioural and emotional features, the Rett Syndrome Behaviour Questionnaire (RSBQ), was developed to test the type and specificity of behavioural features of RS against those found in girls with SMR. Results: After controlling for the effects of RS-related physical disabilities, the RSBQ discriminated between the groups. Some aspects of the behaviours found to be specific to RS are included in the necessary or supportive RS diagnostic criteria, notably hand behaviours and breathing problems. Additional behavioural features were also more frequently reported in the RS than the SMR group, including mood fluctuations and signs of fear/anxiety, inconsolable crying and screaming at night, and repetitive mouth and tongue movements and grimacing. Conclusions: Full validation of the scale requires confirmation of its discriminatory power and reliability with independent samples of individuals with RS and SMR. Further delineation of the specific profile of behaviours seen in RS may help in identification of the function of the MECP2 gene and in improved differential diagnosis and management of individuals with RS. [source] MECP2 mutations in Serbian Rett syndrome patientsACTA NEUROLOGICA SCANDINAVICA, Issue 6 2007A. Djarmati Background,,, Rett syndrome is a severe neurodevelopmental X-linked dominant disorder affecting 1/15,000 girls worldwide. Eight years ago, the MECP2 gene was associated with the devastating clinical features observed in Rett syndrome patients. Objectives,,, To investigate the spectrum and the frequency of MECP2 mutations in Serbian Rett syndrome patients. Patients and methods,,, We screened the MECP2 coding region by conventional mutational screening (single-strand conformation polymorphism/sequencing) in 24 patients of Serbian origin and in their 41 unaffected family members. In search for gene dosage alterations in seemingly mutation-negative girls, we developed a new, specific quantitative PCR method. Results,,, Nineteen patients (79%) carried MECP2 mutations, five of which were novel (one nonsense mutation, one duplication and three deletions). Fourteen previously described disease-causing sequence changes and one polymorphism were also detected. Detailed case reports are given for the carriers of the novel mutations. Large MECP2 rearrangements cause Rett syndrome in a significant number of girls without ,classic' mutations in this gene. Therefore, we developed a specific quantitative PCR method, covering MECP2 exons 3 and 4, which previously has not been used for screening. No dosage alterations of the two exons were found in the four tested mutation-negative girls. Conclusions,,, This is the first genetic study of Rett syndrome in Serbian patients describing the MECP2 mutational and phenotypic spectrum in this population. Detailed clinical descriptions of this ethnically homogeneous patient population add to our knowledge of genotype/phenotype correlations in this severe condition. [source] Germline mosaicism in Rett syndrome identified by prenatal diagnosisCLINICAL GENETICS, Issue 3 2005F Mari Rett syndrome is an X-linked neurodevelopmental dominant disorder that affects almost exclusively girls. The vast majority of cases are sporadic and are caused by de novo mutations in the MECP2 gene, located in Xq28. Only few familial cases have been reported: in four cases, the mother was an asymptomatic carrier and in other four cases, the germline mosaicism in the mother was postulated. Owing to the above reported cases of germline mosaicism, we decided to offer prenatal diagnosis to all expectant mothers with a Rett daughter despite the absence of the causative mutation in parents' blood. We describe here the outcome of the first nine cases of prenatal diagnosis followed by our center. In eight cases, the fetus did not carry the mutation. In one case, the female fetus did carry the same mutation of the affected sister. The couple decided to interrupt the pregnancy and to devolve fetal tissues for research purposes. Our results indicate that prenatal diagnosis should be proposed to all couples with a Rett daughter, even when the mutation is apparently de novo. Moreover, one positive prenatal test among the first nine cases indicates that germline mosaicism may be seriously considered for the assessment of recurrence risk during genetic counseling. [source] | |||||||||||||