Rett syndrome with and without detected MECP2 mutations: an attempt to redefine phenotypes

Background: The diagnosis of Rett syndrome (RTT) is based on a set of clinical criteria, irrespective of mutation status. The aims of this study were (1) to define the clinical differences existing between patients with Rett syndrome with (Group I) and without a MECP2 mutation (Group II), and (2) to characterize the phenotypes associated with the more common MECP2 mutations. Patients and methods: We analyzed 87 patients fulfilling the clinical criteria for RTT. All were observed and videotaped by the same paediatric neurologist. Seven common mutations were considered separately, and associated clinical features analysed. Results: Comparing Group I and II, we found differences concerning psychomotor development prior to onset, acquisition of propositive manipulation and language, and evolving autistic traits. Based on age at observation, we found differences in eye pointing, microcephaly, growth, number of stereotypies, rigidity, ataxia and ataxic-rigid gait, and severity score. Patients with truncating differed from those with missense mutations regarding acquisition of propositive words and independent gait, before the beginning of the disease, and microcephaly, growth, foot length, dystonia, rigidity and severity score, at the time of observation. Patients with the R168X mutation had a more severe phenotype, whereas those with R133C showed a less severe one. Patients with R294X had a hyperactive behaviour, and those with T158M seemed to be particularly ataxic and rigid. Conclusion: A clear regressive period (with loss of prehension and language, deceleration of growth) and the presence of more than three different stereotypies, rigidity and ataxic-rigid gait seemed to be very helpful in differentiating Group I from Group II

Clinical and biological progress over 50 years in Rett syndrome

In the 50 years since Andreas Rett first described the syndrome that came to bear his name, and is now known to be caused by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, a compelling blend of astute clinical observations and clinical and laboratory research has substantially enhanced our understanding of this rare disorder. Here, we document the contributions of the early pioneers in Rett syndrome (RTT) research, and describe the evolution of knowledge in terms of diagnostic criteria, clinical variation, and the interplay with other Rett-related disorders. We provide a synthesis of what is known about the neurobiology of MeCP2, considering the lessons learned from both cell and animal models, and how they might inform future clinical trials. With a focus on the core criteria, we examine the relationships between genotype and clinical severity. We review current knowledge about the many comorbidities that occur in RTT, and how genotype may modify their presentation. We also acknowledge the important drivers that are accelerating this research programme, including the roles of research infrastructure, international collaboration and advocacy groups. Finally, we highlight the major milestones since 1966, and what they mean for the day-to-day lives of individuals with RTT and their families

The character and biological treatability of log pond waters

A study was conducted to determine the chemical nature and the biological treatability of log pond water. Various analyses including total solids, volatile solids, suspended solids, dissolved oxygen, pH, COD, BOD₅, BOD₂₀, total Kjeldahl nitrogen, nitrate nitrogen, phosphate, and PBI were performed on water samples from each of the four ponds studied. Each pond proved to be homogeneous with respect to these analyses. Factors such as log storage time and overflow rate were found to affect the chemical nature of the log ponds. All the ponds had very low five-day biochemical oxygen demand (BOD₅) values in comparison to their respective chemical oxygen demand (COD) values, indicating high concentrations of non-biodegradable substances. The log ponds contained sufficient nitrogen and phosphorus to support biological activity. Two bench scale extended aeration units were used for the biological treatability study. The log pond water was fed to the units h contained acclimated sludge and this mixture was aerated. The aeration units performed quite well and produced similar results, Generally, the longer the detention time, the higher the COD, BOD₅ and PBI removals. However, these removals tended to level off at the five-day detention period so a further increase in detention time would not have increased the removals substantially. The following removals were obtained with a five-day detention time: total COD = 63%, soluble COD = 52%, BOD₅ = 93%, PBI = 64%. The mixed liquor suspended solids (MLSS) level ranged from 380 mg/1 at a five-day contact period to 1060 mg/1 at a one-day contact time. The oxygen uptake of the MLSS was only 3.1 mg 02 per hour gram MLSS. The unitless oxygen transfer parameter, a, was found to be 1. I for log pond water demonstrating that the rate of oxygen transfer into log pond water was greater than into distilled water. The results of this study clearly indicate that log pond water can be effectively treated using aerobic biological processes

Rapid Genotyping of Common MeCP2 Mutations with an Electronic DNA Microchip Using Serial Differential Hybridization

Rett syndrome is a neurodevelopmental disorder that affects females almost exclusively, and in which eight common point mutations on the X-linked MeCP2 gene are knows to cause over 70% of mutation-positive cases. We explored the use of a novel platform to detect the eight common mutations in Rett syndrome patients to expedite and simplify the process of identification of known genotypes. The Nanogen workstation consists of a two-color assay based on electric hybridization and thermal discrimination, all performed on an electronically active NanoChip. This genotyping platform was tested on 362 samples of a pre-determined genotype, which had been previously identified by a combination of DHPLC (denaturing high performance liquid chromatography) and direct sequencing. This genotyping technique proved to be rapid, facile, and displayed a specificity of 100% with 3% ambiguity. In addition, we present consecutive testing of seven mutations on a single pad of the NanoChip. This was accomplished by tagging down two amplimers together and serially hybridizing for seven different loci, allowing us to genotype samples for seven of the eight common Rett mutations on a single pad. This novel method displayed the same level of specificity and accuracy as the single amplimer reactions, and proved to be faster and more economical