TY - JOUR
T1 - MECP2 deletions and genotype-phenotype correlation in Rett syndrome
AU - Scala, Elisa
AU - Longo, Ilaria
AU - Ottimo, Federica
AU - Speciale, Caterina
AU - Sampieri, Katia
AU - Katzaki, Eleni
AU - Artuso, Rosangela
AU - Mencarelli, Maria Antonietta
AU - D'Ambrogio, Tatiana
AU - Vonella, Giuseppina
AU - Zappella, Michele
AU - Hayek, Giuseppe
AU - Battaglia, Agatino
AU - Mari, Francesca
AU - Renieri, Alessandra
AU - Ariani, Francesca
PY - 2007/12/1
Y1 - 2007/12/1
N2 - 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).
AB - 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).
KW - IRAK1
KW - MECP2
KW - Multiplex ligation-dependent probe amplification
KW - Preserved speech variant
KW - Rett syndrome
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U2 - 10.1002/ajmg.a.32002
DO - 10.1002/ajmg.a.32002
M3 - Article
C2 - 17968969
AN - SCOPUS:36849060323
VL - 143
SP - 2775
EP - 2784
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 23
ER -