MECP2 deletions and genotype-phenotype correlation in Rett syndrome

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...

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Published inAmerican journal of medical genetics. Part A Vol. 143A; no. 23; pp. 2775 - 2784
Main Authors Scala, Elisa, Longo, Ilaria, Ottimo, Federica, Speciale, Caterina, Sampieri, Katia, Katzaki, Eleni, Artuso, Rosangela, Mencarelli, Maria Antonietta, D'Ambrogio, Tatiana, Vonella, Giuseppina, Zappella, Michele, Hayek, Giuseppe, Battaglia, Agatino, Mari, Francesca, Renieri, Alessandra, Ariani, Francesca
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2007
Wiley-Liss
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Summary: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.
Bibliography:Telethon Foundation - No. GGP02006; No. GGP05005
ArticleID:AJMG32002
Emma and Ernesto Rulfo Foundation
MIUR - No. FIRB 01; No. PRIN 2005
istex:18F84859E9202FC558A944AC33632D5D9E19DFA8
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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. Am J Med Genet Part A 143A:2775–2784.
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.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.32002