Correlation between MECP2 genotype and phenotype in Chinese patients with Rett syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>Rett syndrome (RTT) is a neurodevelopmental disorder that represents one of the most common genetic causes of mental retardation in girls. The aim of this study was to investigate the correlation between MECP2 genotype and phenotype and thereby not only to provide assistance for clinical care, but also facilitate clinical genetic counseling.</p><p><b>METHOD</b>Individual phenotype characteristic and clinical severity of 126 children with RTT diagnosed by molecular genetic methods were evaluated by using scales of Kerr et al and Scala et al. Statistical package SPSS 12.0 was used for analyses of data. Since the majority of the data were not normally distributed, non-parametric tests were used. The Kruskal-Wallis test/Wilcoxon Mann-Whitney test was employed to compare total severity phenotype scores. The Fisher exact test was used for comparing rates. Statistical significance was set at P < 0.05.</p><p><b>RESULT</b>There were no significant differences in the average overall scores for RTT patients with mutations in the region of methyl-CpG-binding domain (MBD) compared with those mutations in the transcription repression domain (TRD) and C terminal segment (CTS), also patients with nonsense mutations compared with missense mutations, frameshift mutations and large deletions (P > 0.05). The RTT patients with nonsense mutations located in the region of MBD have more severe phenotype than those with missense mutations in the same region (P = 0.016). Among p.T158M, p.R168X, c.806delG and p.R255X, there were no significant differences in the average overall scores (P > 0.05), but there were significant differences in language skill (P = 0.028) and in language impairment rate at different level (P = 0.019).</p><p><b>CONCLUSION</b>There are relationships between MECP2 genotype and phenotype:the RTT patients with nonsense mutations located in MBD tend to develop more severe phenotype;there are significant differences in language skill and language impairment rate in the groups with p.T158M, p.R168X, c.806del and p.R255X, which had higher frequency in children below five-years of age and the p.R168X present with most severe impairment.</p>

MECP2 gene mutations in twenty-six cases with atypical Rett syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>Rett syndrome (RTT) is an X-linked progressive neurodeveopmental disorder that almost exclusively affects girls, and is one of the most common causes of mental retardation in females, with an estimated prevalence of approximately 1 in 10,000 - 15,000 female individuals. Mutations in X-linked methyl-CpG-binding protein 2 (MECP2) gene, located on chromosome Xq28, have been found to be a cause of RS. A lot of mutations have been reported to be related to RS recently. Mutations are found in 70% - 85% of patients with classical RTT and in less than 50% of patients with atypical RS. Up to now, RTT is diagnosed based on a consistent counseling for clinical features and the established diagnostic criteria. The present study aimed to investigate frequency and type of mutation of MECP2 gene and if hot spot of mutation exits in patients with atypical RTT and find out the relationship between genotype and phenotype.</p><p><b>METHODS</b>A systematic analysis of the entire coding region of MECP2 in 26 unrelated patients with atypical RTT was performed by polymerase chain reaction (PCR) and direct sequencing. Genomic DNA was extracted using standard procedures from the peripheral blood leukocytes of each patient. PCR amplification products were checked by 2% agarose gel electrophoresis and were subsequently sequenced with ABI 3730 Automated DNA Sequencer with both the forward and reverse primers. Mutational analyses were performed using normal human genomic MECP2 sequence as a reference (GenBank accession NO.AF030876).</p><p><b>RESULTS</b>Seven mutations were identified in 12 of 26 patients. Most of the mutations were missense mutation; c.397C > T (R133C) was found in 3 of 26 patients; c.473C > T (T158M) and c.916C > T (R306C) were found in 2 of 26 patients, respectively; c.397A > G (R133H) and c.1005G > A (R335C) were found in 1 of 26 patients, respectively. One base pair deletion mutation (806delG) resulting in frameshift was found in 2 of 26 patients, and 1 base pair transversion at splice accept-site (IVS3-2A > T).</p><p><b>CONCLUSION</b>The results of this study indicated that c.397C > T (R133C), c.473C > T (T158M) and c.916C > T (R306C) were hot spot mutations in MECP2 gene of patients with atypical RTT. There was some relationship between genotype and phenotype.</p>