Mutation analysis of the MECP2 gene in patients of Slavic origin with Rett syndrome: novel mutations and polymorphisms.
Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder in females, is caused mainly by de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Here we report mutation analysis of the MECP2 gene in 87 patients with RTT from the Czech and Slovak Republics, and Ukraine. The patients, all girls, with classical RTT were investigated for mutations using bi-directional DNA sequencing and conformation sensitive gel electrophoresis analysis of the coding sequence and exon/intron boundaries of the MECP2 gene. Restriction fragment length polymorphism analysis was performed to confirm the mutations that cause the creation or abolition of the restriction site. Mutation-negative cases were subsequently examined by multiple ligation-dependent probe amplification (MLPA) to identify large deletions. Mutation screening revealed 31 different mutations in 68 patients and 12 non-pathogenic polymorphisms. Six mutations have not been previously published: two point mutations (323T>A, 904C>T), three deletions (189_190delGA, 816_832del17, 1069delAGC) and one deletion/inversion (1063_1236del174;1189_1231inv43). MLPA analysis revealed large deletions in two patients. The detection rate was 78.16%. Our results confirm the high frequency of MECP2 mutations in females with RTT and provide data concerning the mutation heterogeneity in the Slavic population.
Zahorakova
Daniela
D
Department of Pediatrics, First School of Medicine, Charles University, Ke Karlovu 2, 128 08, Prague 2, Czech Republic.
Rosipal
Robert
R
Department of Pediatrics, First School of Medicine, Charles University, Ke Karlovu 2, 128 08, Prague 2, Czech Republic.
Hadac
Jan
J
Department of Child Neurology, Thomayer University Hospital, Prague, Czech Republic.
Zumrova
Alena
A
Department of Child Neurology, University Hospital Motol, Prague, Czech Republic.
Bzduch
Vladimir
V
First Department of Pediatrics, Commenius University Children's Hospital, Bratislava, Slovakia.
Misovicova
Nadezda
N
Department of Clinical Genetics, Martin University Hospital, Martin, Slovakia.
Baxova
Alice
A
Institute of Biology and Clinical Genetics, General University Hospital, Prague, Czech Republic.
Zeman
Jiri
J
Department of Pediatrics, First School of Medicine, Charles University, Ke Karlovu 2, 128 08, Prague 2, Czech Republic.
Martasek
Pavel
P
Department of Pediatrics, First School of Medicine, Charles University, Ke Karlovu 2, 128 08, Prague 2, Czech Republic. pavel.martasek@gmail.com.
D004252:DNA Mutational Analysis; D005061:Europe, Eastern; D005260:Female; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D015518:Rett Syndrome / Q000235:genetics*; D044465:White People / Q000235:genetics
D051783:Methyl-CpG-Binding Protein 2