The methyl CpG binding protein 2 (MECP2), protein that binds to methylated DNA sequences and represses the expression of specific genes, is essential for normal function of mature nerve cells. The protein is encoded by MECP2 gene and its mutations are responsible for approximately 90% of all Rett syndrome (RTT) cases. RTT is a neurodevelopmental disorder that affects mainly girls. Its characteristic features include arrested psychomotor development (6–18 months), congenital impairment, loss of speech, characteristic stereotypical movements, regression of gained skills and other neuropsychiatric abnormalities. Nineteen patients with primary clinical diagnosis of RTT were referred for molecular examination. The analysis of MECP2 gene included direct sequencing of exons 2–4 and deletion/ duplication analysis using MLPA method. In nine patients we have found seven known point mutations, including three nonsense substitutions in four individuals (p.R168X, p.R255X, and p.R270X in 2 cases) and three missense changes leading to amino acids substitutions in the methyl-binding domain (p.R133C, p.K135E, p.T158M) or in the transcriptional repression domain (p.R306C in 2 cases). In three other patients, a partial deletion of MECP2 was found, including a deletion of exons 3 and 4 (encompassing 2 to 67 kb) and two different deletions of exon 4, encompassing 44 bp and 1 to 7.3 kb, respectively. Together, we were able to confirm the clinical diagnosis of Rett syndrome in 12 cases. The significant presence of large deletions encompassing entire exons suggests that the MLPA analysis should be performed as an important part of the molecular diagnosis in Rett syndrome.
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