Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2

@article{Amir1999RettSI,
  title={Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2},
  author={Ruthie E. Amir and Ignatia Van den Veyver and Mimi Wan and Charles Q. Tran and Uta Francke and Huda Y. Zoghbi},
  journal={Nature Genetics},
  year={1999},
  volume={23},
  pages={185-188}
}
Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females, with an incidence of 1 in 10,000–15,000 (ref. 2). Patients with classic RTT appear to develop normally until 6–18 months of age, then gradually lose speech and purposeful hand use, and develop microcephaly, seizures, autism, ataxia, intermittent hyperventilation and stereotypic hand movements. After initial regression, the condition stabilizes and… Expand

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InterventionDiagnostic Test
Observational Clinical Trial
The purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), CDKL5, FOXG1, and individuals with MECP2… Expand
ConditionsCDKL5 Disorder, FOXG1 Syndrome, MECP2 Duplication dIsorder, (+1 more)
Observational Clinical Trial
The overarching purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), RTT-related disorders including… Expand
ConditionsCDKL5, FOXG1 Disorders, MECP2 Duplication, (+1 more)
Mutations in exon 1 of MECP2 are a rare cause of Rett syndrome
TLDR
Gen dosage analysis by Southern hybridisation or multiplex ligation dependent probe amplification has resulted in identification of large genomic deletions of the MECP2 genomic locus in an additional subset of these mutation negative RTT patients. Expand
Mutation analysis of the methyl-CpG binding protein 2 gene (MECP2) in patients with Rett syndrome
TLDR
A mutation analysis in 40 Japanese patients with RTT was carried out to confirm that M ECP2 is the gene responsible for RTT and to detect common mutations in MECP2. Expand
MECP2 mutations and clinical correlations in Greek children with Rett syndrome and associated neurodevelopmental disorders
TLDR
The analysis of the MECP2 gene could provide a diagnostic tool for RTT and non-specific MR research. Expand
Functional characterisation of MeCP2 mutations found in male patients with X linked mental retardation
TLDR
Transient expression assays indicate that potential alterations in MeCP2 function resulting from the A140V and the E137G mutations are different from those associated with mutations observed in Rett syndrome and may explain why the manifestation of Me CP2 related mental disorder in male patients with non-specific X linked mental retardation is clinically distinct from Rett Syndrome. Expand
Evidence of somatic mosaicism for aMECP2 mutation in females with Rett syndrome: diagnostic implications
TLDR
M mosaicism for a somatic MECP2 mutation found in two unrelated females affected with RTT is reported for the first time. Expand
Submicroscopic duplication in Xq28 causes increased expression of the MECP2 gene in a boy with severe mental retardation and features of Rett syndrome
Rett syndrome is an X linked mental retardation syndrome almost exclusively affecting girls, and has long been regarded as an X linked dominant condition lethal in hemizygous males.1 Mutations in theExpand
Rett syndrome: methyl-CpG-binding protein 2 mutations and phenotype-genotype correlations.
TLDR
MECP2 mutations thus manifest in a far broader array of phenotypes than classic RTT, which should prove helpful in diagnosing cases of mild learning disability or severe neonatal encephalopathy of unknown cause and also should provide insight into the pathogenesis of RTT. Expand
Mutational analysis of the MECP2 gene in Japanese patients with Rett syndrome
TLDR
The novel disease alleles and benign variants of the MECP2 gene found in this study should contribute to the establishment of a reliable diagnosis of Rett syndrome. Expand
Screening of MECP2 coding sequence in patients with phenotypes of decreasing likelihood for Rett syndrome: a cohort of 171 cases
TLDR
The fully developed clinical picture is dominated by mental retardation, reduction of communication skills, and loss of purposeful hand movements combined with hand stereotypes, progressive microcephaly, abnormal locomotion, and other various minor signs. Expand
Spectrum of mutations in the MECP2 gene in patients with infantile autism and Rett syndrome
TLDR
Using a systematic gene screening approach, mutations in the MECP2 gene, which encodes methyl-CpG binding protein 2, are identified as the cause of some RTT cases, suggesting that RTT is an X linked dominant mutation with lethality in hemizygous males. Expand
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References

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A new Rett syndrome family consistent with X-linked inheritance expands the X chromosome exclusion map.
TLDR
The X chromosome inactivation (XCI) patterns in the female members of a newly identified family with recurrence of RTT in a maternal aunt and a niece are investigated, supporting the hypothesis that RTT is an X-linked disorder. Expand
Candidate gene analysis in Rett syndrome and the identification of 21 SNPs in Xq.
TLDR
The genomic characterization of GLUR3 and GABRA3 will allow mutational analysis of these genes as candidates for other X-linked neurological disorders mapping to Xq25-Xq26 and Xq28. Expand
Evaluation of two X chromosomal candidate genes for Rett syndrome: glutamate dehydrogenase-2 (GLUD2) and rab GDP-dissociation inhibitor (GDI1).
TLDR
Two candidate genes, GLUD2 and GDI1, chosen because of their expression patterns and functions in the central nervous system and their location in the nonexcluded region of Xq, can be excluded as candidate genes for this syndrome. Expand
Patterns of X chromosome inactivation in the rett syndrome
TLDR
Analysis of leukocyte DNA from a mother of two affected half-sisters revealed non-random X chromosome inactivation suggesting a possible selection against RS allele, the first evidence to support the hypothesis of an X linked mutation which is lethal in males. Expand
Examination of X chromosome markers in Rett syndrome: exclusion mapping with a novel variation on multilocus linkage analysis.
TLDR
Using the exclusion criterion of a lod score less than -2, this study was able to exclude the region between the Duchenne muscular dystrophy locus and the DXS456 locus, which will result in a defined region of the X chromosome that should be searched for candidate sequences for the Rett syndrome gene in both familial and sporadic cases. Expand
A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: Report of 35 cases
TLDR
The exclusive involvement of females, correlated with findings in family data analyses, suggests a dominant mutation on one X chromosome that results in affected girls and nonviable male hemizygous conceptuses. Expand
Rett syndrome: confirmation of X-linked dominant inheritance, and localization of the gene to Xq28.
TLDR
The authors thank Mark Lanasa, for assistance with the X-inactivation studies, and Paco Murillo-Martinez, for help with linkage analyses. Expand
Genetic Aspects of Rett Syndrome
  • H. Zoghbi
  • Medicine
  • Journal of child neurology
  • 1988
TLDR
Hypotheses about the genetic mechanisms involved in this syndrome along with suggestions to approach the molecular basis of this disorder are presented. Expand
The methyl-CpG binding protein MeCP2 is essential for embryonic development in the mouse
TLDR
The results demonstrate that MeCP2, like DMA methyltransferase7, is dispensable in stem cells, but essential for embryonic development. Expand
Rett's Syndrome: Prevalence and Impact on Progressive Severe Mental Retardation in Girls
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  • Medicine
  • Acta paediatrica Scandinavica
  • 1985
TLDR
It is concluded that Rett's syndrome should be considered as an aetiological factor to think of in females within this group of severely mentally retarded persons of this age group in central Sweden. Expand
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