Maternal mosaicism for mutations in the ARX gene in a family with X linked mental retardation

International audienceWe describe two brothers with mental retardation (MR) due to a c.428_451dup24 in the ARX gene. The mother did not apparently carry the mutation, as determined by dHPLC and by fragment size analysis. Using semiquantitative fluorescent PCR, we show however that 4% of her lymphocytes and 24% of her fibroblasts harbored the duplication. We thus show that the mother displays somatic mosaicism for the duplication thereby highlighting the need to reconsider the molecular screening in sporadic cases of MR

High frequency-low loss SAW resonators built on NanoCrystalline Diamond-based substrate

International audienceThe interest of surface acoustic wave devices (SAW) operating in radio-frequency range is their very high compactness, low losses and high quality factor. Thus, they are very interesting components for the stabilization of ultra-low noise on-board oscillators operating in direct bands. The need for working frequency beyond 3 GHz has lead SAW manufacturers to develop multilayer diamond-based waveguides providing higher phase velocity than conventional single-crystal materials, typically ranging from 7 to 12 km.s-1 for elliptically polarized waves. The very problem in this approach is the excitation and detection of acoustic waves requiring a high quality piezoelectric layer of less than one micrometer thick with physical properties as close as possible to the tabulated ones. An ultimate control of the film thickness and roughness is required to control dispersion and diffusion losses. In this work, we investigated a structure based on Nano-Crystalline Diamond (NCD). The waves are launched and detected using a Zinc Oxide film deposited atop the diamond layer, yielding notable dispersive properties of the device. In this way, technological developments have been achieved (NCD growth, piezoelectric layer deposition, e-beam and optical lithography) to build SAW devices taking advantage of NCD films to try and benefit from their suspected low acoustic damping. Results show the possibility of developing devices operating between 2 and 3 GHz at minimum, having losses lower than 10 dB. At last, devices whose dimensions are compatible with conventional lithography processes, show resonances at more than 4 GHz with less than 8 dB of insertion loss, what is, at the knowledge of the authors, the best experimental result for such devices. To compare with previous results, a device operating near 3 GHz has been used to stabilize an oscillator. Short term stability has been measured at 10-8 s-1 and a phase noise floor was observed at -170 dB at 3 MHz from the carrier. Although not yet meeting the expected requirements, these results show the impact of loss reduction and general device improvement and allow for preparing future work near 5 GHz

The DM-scope registry: a rare disease innovative framework bridging the gap between research and medical care

International audienceBackground: The relevance of registries as a key component for developing clinical research for rare diseases (RD) and improving patient care has been acknowledged by most stakeholders. As recent studies pointed to several limitations of RD registries our challenge was (1) to improve standardization and data comparability; (2) to facilitate interoperability between existing RD registries; (3) to limit the amount of incomplete data; (4) to improve data quality. This report describes the innovative concept of the DM-Scope Registry that was developed to achieve these objectives for Myotonic Dystrophy (DM), a prototypical example of highly heterogeneous RD. By the setting up of an integrated platform attractive for practitioners use, we aimed to promote DM epidemiology, clinical research and patients care management simultaneously.Results: The DM-Scope Registry is a result of the collaboration within the French excellence network established by the National plan for RDs. Inclusion criteria is all genetically confirmed DM individuals, independently of disease age of onset. The dataset includes social-demographic data, clinical features, genotype, and biomaterial data, and is adjustable for clinical trial data collection. To date, the registry has a nationwide coverage, composed of 55 neuromuscular centres, encompassing the whole disease clinical and genetic spectrum. This widely used platform gathers almost 3000 DM patients (DM1 n = 2828, DM2 n = 142), both children (n = 322) and adults (n = 2648), which accounts for > 20% of overall registered DM patients internationally. The registry supported 10 research studies of various type i.e. observational, basic science studies and patient recruitment for clinical trials.Conclusion: The DM-Scope registry represents the largest collection of standardized data for the DM population. Our concept improved collaboration among health care professionals by providing annual follow-up of quality longitudinal data collection. The combination of clinical features and biomolecular materials provides a comprehensive view of the disease in a given population. DM-Scope registry proves to be a powerful device for promoting both research and medical care that is suitable to other countries. In the context of emerging therapies, such integrated platform contributes to the standardisation of international DM research and for the design of multicentre clinical trials. Finally, this valuable model is applicable to other RDs

The DM-scope registry: a rare disease innovative framework bridging the gap between research and medical care

International audienceBackground: The relevance of registries as a key component for developing clinical research for rare diseases (RD) and improving patient care has been acknowledged by most stakeholders. As recent studies pointed to several limitations of RD registries our challenge was (1) to improve standardization and data comparability; (2) to facilitate interoperability between existing RD registries; (3) to limit the amount of incomplete data; (4) to improve data quality. This report describes the innovative concept of the DM-Scope Registry that was developed to achieve these objectives for Myotonic Dystrophy (DM), a prototypical example of highly heterogeneous RD. By the setting up of an integrated platform attractive for practitioners use, we aimed to promote DM epidemiology, clinical research and patients care management simultaneously.Results: The DM-Scope Registry is a result of the collaboration within the French excellence network established by the National plan for RDs. Inclusion criteria is all genetically confirmed DM individuals, independently of disease age of onset. The dataset includes social-demographic data, clinical features, genotype, and biomaterial data, and is adjustable for clinical trial data collection. To date, the registry has a nationwide coverage, composed of 55 neuromuscular centres, encompassing the whole disease clinical and genetic spectrum. This widely used platform gathers almost 3000 DM patients (DM1 n = 2828, DM2 n = 142), both children (n = 322) and adults (n = 2648), which accounts for > 20% of overall registered DM patients internationally. The registry supported 10 research studies of various type i.e. observational, basic science studies and patient recruitment for clinical trials.Conclusion: The DM-Scope registry represents the largest collection of standardized data for the DM population. Our concept improved collaboration among health care professionals by providing annual follow-up of quality longitudinal data collection. The combination of clinical features and biomolecular materials provides a comprehensive view of the disease in a given population. DM-Scope registry proves to be a powerful device for promoting both research and medical care that is suitable to other countries. In the context of emerging therapies, such integrated platform contributes to the standardisation of international DM research and for the design of multicentre clinical trials. Finally, this valuable model is applicable to other RDs

Targeted therapy in patients with PIK3CA-related overgrowth syndrome

International audienc