Investigating genotype-phenotype relationships in Rett syndrome using an international data set

Bebbington, A., Anderson, A., Ravine, D., Fyfe, S., Pineda, M., De Klerk, N., Ben-Zeev, B., Yatawara, N., Percy, A., Kaufmann, W. E. and Leonard, H. (2008) Investigating genotype-phenotype relationships in Rett syndrome using an international data set. Neurology, 70 11: 868-875. doi:10.1212/

Author Bebbington, A.
Anderson, A.
Ravine, D.
Fyfe, S.
Pineda, M.
De Klerk, N.
Ben-Zeev, B.
Yatawara, N.
Percy, A.
Kaufmann, W. E.
Leonard, H.
Title Investigating genotype-phenotype relationships in Rett syndrome using an international data set
Journal name Neurology   Check publisher's open access policy
ISSN 0028-3878
Publication date 2008-03-11
Sub-type Article (original research)
DOI 10.1212/
Open Access Status Not Open Access
Volume 70
Issue 11
Start page 868
End page 875
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
BACKGROUND: Rett syndrome is an uncommon neurodevelopmental disorder with an incidence of 1:9,000 live female births. The principal genetic cause was first reported in 1999 when the association with mutations in the methyl-CpG-binding protein 2 (or MECP2) gene was identified. This study uses data from a large international database, InterRett, to examine genotype-phenotype relationships and compares these with previous findings in a population-based cohort. METHOD: The data set for these analyses was derived from a subset of InterRett cases with subject information collected from the family, the clinician, or both. Individual phenotypic characteristics and clinical severity using three scales were compared among those with eight known recurrent pathogenic MECP2 mutations as well as those with C-terminal deletions (n = 272).
RESULTS: Overall, p.R270X and p.R255X were the most severe and p.R133C and p.R294X were the mildest mutations. Significant differences by mutation were seen for individual phenotypic characteristics such as hand use, ambulation, and language.
CONCLUSIONS: This multicenter investigation into the phenotypic correlates of MECP2 mutations in Rett syndrome has provided a greater depth of understanding than hitherto available about the specific phenotypic characteristics associated with commonly occurring mutations. Although the modifying influence of X inactivation on clinical severity could not be included in the analysis, the findings confirm clear genotype-phenotype relationships in Rett syndrome and show the benefits of collaboration crucial to effective research in rare disorders.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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