Linked Life Data

19365833

Source:http://linkedlifedata.com/resource/pubmed/id/19365833

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-5-4
pubmed:abstractText
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. Recently, a new MeCP2 isoform was described, MeCP2_e1, which skips exon 2 and has an alternative N-terminus, translated from exon 1, whereas MeCP2_e2 is translated from a start codon in exon 2. Since the incorporation of exon 1 into standard sequencing protocols for RTT, few exon 1 mutations have been described and are thus assumed to be only rare causes of RTT. Also, studies have suggested that the frameshift mutations identified in exon 1 affect both isoforms. Our aim in this study was to assess the frequency of mutations in exon 1, their relationship to phenotype, and the implications on the etiological role for the isoform MeCP2_e1 in RTT, versus the previously described isoform, MeCP2_e2. We sequenced MECP2 in 51 females with various clinical presentations, including developmental delay, autism, atypical and classical RTT, referred to our laboratories for testing. In patients with identified mutations, X-chromosome inactivation was analyzed. We identified four patients with exon 1 mutations; three were novel (c.1A > T; c.1A > G; c.5C > T), two of which affected the start codon, one a missense change, and one patient had a previously reported splice site mutation, c.62 + 1delGT. The four patients fit criteria for classical RTT, and thus these findings add support to previous reports that exon 1 mutations may be associated with a severe phenotype. Also, these findings add significant weight to the mounting evidence suggesting that the MeCP2_e1 isoform is the etiologically relevant form of the protein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1552-4833
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
149A
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1019-23
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Novel exon 1 mutations in MECP2 implicate isoform MeCP2_e1 in classical Rett syndrome.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, The Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA. csaunders@cmh.edu
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't