Abstract
Among cases in the Australian Rett Syndrome Database, the nonsense mutation p.R270X is one of the most commonly occurring single pathogenic MECP2 mutations. In two recent published reports of the MECP2 mutational spectrum the p.R270X appeared to be under represented. We hypothesised that increased mortality arising from this mutation may underlie this apparent discrepancy. We investigated our hypothesis in two independent study groups from Australia and the UK with prospective data collections (total n=524). Only females with Rett syndrome and an identified MECP2 mutation were included. Significant differences in survival were detected among Rett syndrome cases grouped for the eight most frequent mutations (log-rank χ2 (7)=15.71, P=0.03). Moreover, survival among cases with p.R270X, when compared with survival among cases with all the other mutations was reduced (log-rank χ2 (2)=6.94, P=0.01). Our observation of a reduced survival associated with the p.R270X mutation offers an explanation for the under representation of p.R270X in older subjects with Rett syndrome.
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Acknowledgements
We acknowledge the National Institute of Child Health and Human Development for its current funding of the Australian Rett Syndrome Database under NIH Grant number 1 R01 HD43100-01A1 PI and the Financial Markets Foundation for Children and the Rett Syndrome Australian Research Fund for previous funding. HL is funded by NHMRC program Grant 353514. JC is funded by NHMRC project Grants 185202 and 346603. HA is funded by The Health Foundation, AK and MB by the Rett Syndrome Association UK and MB by the Rett Syndrome Research Foundation, the International Rett Syndrome Association, the Rett Syndrome Association Scotland and the Scottish Hospital Endowments Research Trust. We express our gratitude to all the families who have participated in the study; the Australian Paediatric Surveillance Unit and the Rett Syndrome Association of Australia who facilitated case ascertainment in Australia. In addition, we thank the Rett Syndrome Association UK and the regional genetics and paediatrics services, which have all strongly supported Rett syndrome research in the United Kingdom.
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Jian, L., Archer, H., Ravine, D. et al. p.R270X MECP2 mutation and mortality in Rett syndrome. Eur J Hum Genet 13, 1235–1238 (2005). https://doi.org/10.1038/sj.ejhg.5201479
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DOI: https://doi.org/10.1038/sj.ejhg.5201479
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