What does the nature of the MECP2 mutation tell us about parental origin and recurrence risk in Rett syndrome?
Article first published online: 20 JAN 2012
© 2011 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 82, Issue 6, pages 526–533, December 2012
How to Cite
Zhang, J., Bao, X., Cao, G., Jiang, S., Zhu, X., Lu, H., Jia, L., Pan, H., Fehr, S., Davis, M., Leonard, H., Ravine, D. and Wu, X. (2012), What does the nature of the MECP2 mutation tell us about parental origin and recurrence risk in Rett syndrome?. Clinical Genetics, 82: 526–533. doi: 10.1111/j.1399-0004.2011.01838.x
- Issue published online: 6 NOV 2012
- Article first published online: 20 JAN 2012
- Accepted manuscript online: 19 DEC 2011 02:10PM EST
- Received 5 September 2011, revised and accepted for publication 15 December 2011
- mutation bias;
- parental origin;
- Rett syndrome
Zhang J, Bao X, Cao G, Jiang S, Zhu X, Lu H, Jia L, Pan H, Fehr S, Davis M, Leonard H, Ravine D, Wu X. What does the nature of the MECP2 mutation tell us about parental origin and recurrence risk in Rett syndrome?
The MECP2 mutations occurring in the severe neurological disorder Rett syndrome are predominantly de novo, with rare familial cases. The aims of this study were to provide a precise estimate of the parental origin of MECP2 mutations using a large Chinese sample and to assess whether parental origin varied by mutation type. The parental origin was paternal in 84/88 [95.5%, (95% confidence interval 88.77–98.75)] of sporadic Chinese cases. However, in a pooled sample including data from the literature the spectrum of mutations occurring on maternally and paternally derived chromosomes differed significantly. The excess we found of ‘single base pair gains or losses' on maternally derived MECP2 gene alleles suggests that this mutational category is associated with an elevated risk of gonadal mosaicism, which has implications for genetic counseling.