Document Detail


Updating the profile of C-terminal MECP2 deletions in Rett syndrome.
MedLine Citation:
PMID:  19914908     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: This study aimed to compare the phenotype of Rett syndrome cases with C-terminal deletions to that of cases with different MECP2 mutations and to examine the phenotypic variation within C-terminal deletions.
METHODS: Cases were selected from InterRett, an international database and from the population-based Australian Rett Syndrome Database. Cases (n=832) were included if they had a pathogenic MECP2 mutation in which the nature of the amino acid change was known. Three severity scale systems were used, and individual aspects of the phenotype were also compared.
RESULTS: Lower severity was associated with C-terminal deletions (n=79) compared to all other MECP2 mutations (e.g. Pineda scale C-terminals mean 15.0 (95% CI 14.0-16.0) vs 16.2 (15.9-16.5). Cases with C-terminal deletions were more likely to have a normal head circumference (odds ratio 3.22, 95% CI 1.53 - 6.79) and weight (odds ratio 2.97, 95% CI 1.25-5.76). Onset of stereotypies tended to be later (median age 2.5 years vs 2 years, p<0.001 from survival analysis), and age of learning to walk tended to be earlier (median age 1.6 years vs 2 years, p=0.002 from survival analysis). Those with C-terminal deletions occurring later in the region had lower average severity scores than those occurring earlier in the region.
CONCLUSION: In terms of overall severity C-terminal deletion cases would appear to be in the middle of the range. In terms of individual aspects of phenotype growth and ability to ambulate appear to be particular strengths. By pooling data internationally this study has achieved the case numbers to provide a phenotypic profile of C-terminal deletions in Rett syndrome.
Authors:
A Bebbington; A Percy; J Christodoulou; D Ravine; G Ho; P Jacoby; A Anderson; M Pineda; B Ben Zeev; N Bahi-Buisson; E Smeets; H Leonard
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-11-12
Journal Detail:
Title:  Journal of medical genetics     Volume:  47     ISSN:  1468-6244     ISO Abbreviation:  J. Med. Genet.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-23     Completed Date:  2010-07-28     Revised Date:  2011-01-03    
Medline Journal Info:
Nlm Unique ID:  2985087R     Medline TA:  J Med Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  242-8     Citation Subset:  IM    
Affiliation:
Telethon Institute for Child Health Research, Australia.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Chi-Square Distribution
Child
Child, Preschool
Databases, Factual
Gene Deletion*
Humans
Infant
Methyl-CpG-Binding Protein 2 / genetics*
Middle Aged
Multivariate Analysis
Phenotype
Rett Syndrome / genetics*,  pathology
Severity of Illness Index
Grant Support
ID/Acronym/Agency:
5R01HD043100-05/HD/NICHD NIH HHS; R01 HD043100-05/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/MECP2 protein, human; 0/Methyl-CpG-Binding Protein 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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