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 in | American journal of medical genetics. Part A Vol. 143A; no. 23; pp. 2775 - 2784 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.12.2007
Wiley-Liss |
Subjects | |
Online Access | Get full text |
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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. |
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Bibliography: | Telethon Foundation - No. GGP02006; No. GGP05005 ArticleID:AJMG32002 Emma and Ernesto Rulfo Foundation MIUR - No. FIRB 01; No. PRIN 2005 istex:18F84859E9202FC558A944AC33632D5D9E19DFA8 University of Siena - No. PAR 2001; No. PAR 2002; No. PAR 2004 ark:/67375/WNG-W7K865F3-F 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 |