Linked Life Data

10508514

Source:http://linkedlifedata.com/resource/pubmed/id/10508514

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-10-19
pubmed:abstractText
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 patients usually survive into adulthood. As RTT occurs almost exclusively in females, it has been proposed that RTT is caused by an X-linked dominant mutation with lethality in hemizygous males. Previous exclusion mapping studies using RTT families mapped the locus to Xq28 (refs 6,9,10,11). Using a systematic gene screening approach, we have identified mutations in the gene (MECP2 ) encoding X-linked methyl-CpG-binding protein 2 (MeCP2) as the cause of some cases of RTT. MeCP2 selectively binds CpG dinucleotides in the mammalian genome and mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A (refs 12,13). In 5 of 21 sporadic patients, we found 3 de novo missense mutations in the region encoding the highly conserved methyl-binding domain (MBD) as well as a de novo frameshift and a de novo nonsense mutation, both of which disrupt the transcription repression domain (TRD). In two affected half-sisters of a RTT family, we found segregation of an additional missense mutation not detected in their obligate carrier mother. This suggests that the mother is a germline mosaic for this mutation. Our study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
185-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10508514-Amino Acid Sequence, pubmed-meshheading:10508514-Base Sequence, pubmed-meshheading:10508514-Chromosomal Proteins, Non-Histone, pubmed-meshheading:10508514-DNA, pubmed-meshheading:10508514-DNA Mutational Analysis, pubmed-meshheading:10508514-DNA-Binding Proteins, pubmed-meshheading:10508514-Family Health, pubmed-meshheading:10508514-Female, pubmed-meshheading:10508514-Genetic Linkage, pubmed-meshheading:10508514-Humans, pubmed-meshheading:10508514-Male, pubmed-meshheading:10508514-Methyl-CpG-Binding Protein 2, pubmed-meshheading:10508514-Molecular Sequence Data, pubmed-meshheading:10508514-Mutation, pubmed-meshheading:10508514-Pedigree, pubmed-meshheading:10508514-Point Mutation, pubmed-meshheading:10508514-Repressor Proteins, pubmed-meshheading:10508514-Rett Syndrome, pubmed-meshheading:10508514-Sequence Homology, Amino Acid, pubmed-meshheading:10508514-X Chromosome
pubmed:year
1999
pubmed:articleTitle
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
pubmed:affiliation
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't