Direct Non-Invasive Measuring Techniques ofNanometric Liquid Level Variations UsingExtrinsic Fiber Fabry–Perot Interferometers

International audienceThis article investigates two different non-contact non-invasive solutions for measuring nanometric-order liquid-surface displacements with Extrinsic FiberFabry-Perot interferometers. They are investigated fordeveloping hydrostatic leveling sensor (HLS) systemstargeting the detection of very slowly-evolving movementsin geophysics and geotechnics. In the first technique,the sensing beam from the interferometer traverses a liquidof known refractive index and is reflected by a mirrorsubmerged at the bottom of the HLS vessel. The liquid-levelvariation is thus sensed as a variation of the optical pathlength of the interrogating beam. The second solution, on theother hand, directly exploits the reflection of the sensingbeam at the air-liquid interface in the absence of a reflective surface in the vessel. The subsequent variation of liquid levelis then measured directly as the beam’s optical path variation in air. The common denominator of these two techniquesis an Extrinsic Fabry-Perot sensor with nanometric precision operating at a wavelength of∼1310 nm. The interrogatingbeam suffers from high IR absorption in water, hence the latter solution is more advantageous in terms of dynamicrange. In applications where liquids other than water canbe employed, the use of low optical absorption liquids suchas Polydimethylsiloxanic fluids is recommended at this operating wavelength. Being more viscous and less volatile thanwater, these fluids can significantly improve the noise floor of HLS systems, hence contributing to a larger dynamicrange, lower instrumental drift and higher signal-to-noise ratio

How silence shapes the brain: synonymous variants alter codon usage and translation of Sonic Hedgehog in holoprosencephaly

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Genetics of neural tube defects: new candidate genes and complex mode of inheritance

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Integrated clinical and omics approach to rare diseases novel genes and oligogenic inheritance in holoprosencephaly

International audienceHoloprosencephaly is a pathology of forebrain development characterized by high phenotypic heterogeneity. The disease presents with various clinical manifestations at the cerebral or facial levels. Several genes have been implicated in holoprosencephaly but its genetic basis remains unclear different transmission patterns have been described including autosomal dominant, recessive and digenic inheritance. Conventional molecular testing approaches result in a very low diagnostic yield and most cases remain unsolved. In our study, we address the possibility that genetically unsolved cases of holoprosencephaly present an oligogenic origin and result from combined inherited mutations in several genes. Twenty-six unrelated families, for whom no genetic cause of holoprosencephaly could be identified in clinical settings [whole exome sequencing and comparative genomic hybridization (CGH)-array analyses], were reanalysed under the hypothesis of oligogenic inheritance. Standard variant analysis was improved with a gene prioritization strategy based on clinical ontologies and gene co-expression networks. Clinical phenotyping and exploration of cross-species similarities were further performed on a family-by-family basis. Statistical validation was performed on 248 ancestrally similar control trios provided by the Genome of the Netherlands project and on 574 ancestrally matched controls provided by the French Exome Project. Variants of clinical interest were identified in 180 genes significantly associated with key pathways of forebrain development including sonic hedgehog (SHH) and primary cilia. Oligogenic events were observed in 10 families and involved both known and novel holoprosencephaly genes including recurrently mutated FAT1, NDST1, COL2A1 and SCUBE2. The incidence of oligogenic combinations was significantly higher in holoprosencephaly patients compared to two control populations (P < 10-9). We also show that depending on the affected genes, patients present with particular clinical features. This study reports novel disease genes and supports oligogenicity as clinically relevant model in holoprosencephaly. It also highlights key roles of SHH signalling and primary cilia in forebrain development. We hypothesize that distinction between different clinical manifestations of holoprosencephaly lies in the degree of overall functional impact on SHH signalling. Finally, we underline that integrating clinical phenotyping in genetic studies is a powerful tool to specify the clinical relevance of certain mutations