How to cite this article: Scala E, Longo I, Ottimo F, Speciale C, Sampieri K, Katzaki E, Artuso R, Mencarelli MA, D'Ambrogio T, Vonella G, Zappella M, Hayek G, Battaglia A, Mari F, Renieri A, Ariani F. 2007. MECP2 deletions and genotype–phenotype correlation in Rett syndrome. Am J Med Genet Part A 143A:2775–2784.
MECP2 deletions and genotype–phenotype correlation in Rett syndrome†
Article first published online: 29 OCT 2007
Copyright © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 143A, Issue 23, pages 2775–2784, 1 December 2007
How to Cite
Scala, E., Longo, I., Ottimo, F., Speciale, C., Sampieri, K., Katzaki, E., Artuso, R., Mencarelli, M. A., D'Ambrogio, T., Vonella, G., Zappella, M., Hayek, G., Battaglia, A., Mari, F., Renieri, A. and Ariani, F. (2007), MECP2 deletions and genotype–phenotype correlation in Rett syndrome. Am. J. Med. Genet., 143A: 2775–2784. doi: 10.1002/ajmg.a.32002
- Issue published online: 27 NOV 2007
- Article first published online: 29 OCT 2007
- Manuscript Accepted: 7 JUN 2007
- Manuscript Received: 14 NOV 2006
- Telethon Foundation. Grant Numbers: GGP02006, GGP05005
- Emma and Ernesto Rulfo Foundation
- MIUR. Grant Numbers: FIRB 01, PRIN 2005
- University of Siena. Grant Numbers: PAR 2001, PAR 2002, PAR 2004
- Rett syndrome;
- multiplex ligation-dependent probe amplification;
- preserved speech variant
Rett syndrome is a neurodevelopmental disorder that represents one of the most common genetic causes of mental retardation in girls. MECP2 point mutations in exons 2–4 account for about 80% of classic Rett cases and for a lower percentage of variant patients. We investigated the genetic cause in 77 mutation-negative Rett patients (33 classic, 31 variant, and 13 Rett-like cases) by searching missed MECP2 defects. DHPLC analysis of exon 1 and MLPA analysis allowed us to identify the defect in 17 Rett patients: one exon 1 point mutation (c.47_57del) in a classic case and 16 MECP2 large deletions (15/33 classic and 1/31 variant cases). One identical intragenic MECP2 deletion, probably due to gonadal mosaicism, was found in two sisters with discordant phenotype: one classic and one “highly functioning” preserved speech variant. This result indicates that other epigenetic or genetic factors, beside MECP2, may contribute to phenotype modulation. Three out of 16 MECP2 deletions extend to the adjacent centromeric IRAK1 gene. A putative involvement of the hemizygosity of this gene in the ossification process is discussed. Finally, results reported here clearly indicate that MECP2 large deletions are a common cause of classic Rett, and MLPA analysis is mandatory in MECP2-negative patients, especially in those more severely affected (P = 0.044). © 2007 Wiley-Liss, Inc.