Browsing by Subject "Rett syndrome."

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Open Access
Analysis of MECP2 gene mutations in Rett syndrome patients
(2001) Sayı, Ayça
Rett Syndrome (RTT) is a progressive X-linked dominant childhood neurodevelopmental disorder, affecting 1/10,000-15,000 girls. The disease-causing gene was identified as MECP2 on chromosome Xq28, and mutations have been found in approximately 80% of patients diagnosed with RTT. We screened for eight recurrent MECP2 mutations (R106W, P152R, T158M, R306C, R168X), one rare mutation (F155S) and one polymorphism (E397K) in 63 RTT patients divided into four groups as classic-RTT (n=43), variant-RTT (n=14), male-RTT (n=4), and familial-RTT (n=2). We identified the recurrent mutations in 18 cases. These are three R106W, two P152R, five T158M, five R306C, and three R270X mutations. R168X and F155S were not detected in our patients. Only one patient had the E397K polymorphism who also had the R306C mutation. All these mutations were confirmed via sequencing analysis. In exon 4 of MECP2, several deletion types of mutations are known. By PCR analysis, two patients were found to have an approximately 44 bp deletion in exon 4. Also, a novel mutation – T197M– was identified in one of the patients. We identified a boy affected by RTT who is mosaic for the R270X mutation, and had a normal male karyotype. This result show that a recurrent MECP2 mutation could lead to a similar phenotype in females and males, if the male is a mosaic for the mutation in his somatic cells. MECP2 mutation frequency for the four groups is as follows: 37.2% for the classic-RTT, 28.57% for the variantRTT, and 25% for the male-RTT groups. No mutation was found in the familial group. We could not find a consistent correlation between the clinical symptoms and the type of mutations or the X chromosome inactivation patterns of the patients.
Open Access
In silico identification of candidate MECP2 targets and quantitative analysis in rett syndrome
(2006) Onat, Onur Emre
Rett syndrome (RTT) is an X-linked neuro-developmental disorder seen exclusively girls in the childhood. It is one of the most common causes of mental retardation with an incidence rate of 1/10,000-1/15,000. Mutations in MECP2 gene was described as a common cause of RTT. MECP2 is a transcriptional repressor that regulates gene expression. It is not fully understood which MECP2 targets are affected in RTT and therefore contribute to disease pathogenesis. Researchers approached the problem in two directions: a) Global expression profile analysis and b) Candidate gene analysis. Global expression profile analysis revealed which a limited number of genes including those on the X-chromosome are de-regulated. Candidate gene analysis studies showed that loss of imprinting as exemplified by DLX5 could also contribute to disease pathogenesis. We hypothesize that Xchromosome inactivation (XCI) is an important physiological epigenetic mechanism that could be involved in Rett pathogenesis. We predicted a MECP2 binding motif by a distinctive bioinformatic approach. Using this algorithm we searched for the candidate MECP2 target genes on the X-chromosome and whole genome. The genes FHL1 and MPP1, whose interaction with MECP2 were heuristically displayed were predicted by our algorithm. We identified more than 100 genes which are on the Xchromosome. 10 genes from the list were selected according to their MECP2 binding homology score and X-inactivation status. In order to test this hypothesis we analyzed these genes with quantitative RT-PCR .We expect to identify the key genes that potentially contribute to RTT pathogenesis via disturbances in X-chromosome inactivation.