MECP2 deletions and genotype-phenotype correlation in Rett syndrome

Elisa Scala, Ilaria Longo, Federica Ottimo, Caterina Speciale, Katia Sampieri, Eleni Katzaki, Rosangela Artuso, Maria Antonietta Mencarelli, Tatiana D'Ambrogio, Giuseppina Vonella, Michele Zappella, Giuseppe Hayek, Agatino Battaglia, Francesca Mari, Alessandra Renieri, Francesca Ariani

Research output: Contribution to journalArticlepeer-review


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-negatwe patients, especially in those more severely affected (P = 0.044).

Original languageEnglish
Pages (from-to)2775-2784
Number of pages10
JournalAmerican Journal of Medical Genetics, Part A
Issue number23
Publication statusPublished - Dec 1 2007


  • IRAK1
  • MECP2
  • Multiplex ligation-dependent probe amplification
  • Preserved speech variant
  • Rett syndrome

ASJC Scopus subject areas

  • Genetics(clinical)


Dive into the research topics of 'MECP2 deletions and genotype-phenotype correlation in Rett syndrome'. Together they form a unique fingerprint.

Cite this