Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies

Ethylene hydrogenation and H-D exchange mechanisms over polycrystalline platinum : Influence of sulfur

The rate determining step of the hydrogenation of ethylene on polycrystalline platinum is identified, depending on the hydrogen pressure regime. To account for the kinetic orders with respect to hydrogen as well for the H2 dissociation and recombination as for the C2H4 hydrogenation, the existence of two different sites for hydrogen adsorption is proposed, and the one involved in both reactions proved to be affected by sulfur adsorbed on the metal

Sulfuration du phosphure d' indium et caractérisations électrochimiques

In this paper is studied the thermal sulphidation of low doped (N D ~ 1016 cm-3) N type Indium phosphide in a H2S/H2 vapor at 280 °C. The growth of sulphur layers has been characterized by AES, RHEED and radiotracer measurements using S 35. Electrical characteristics were investigated by capacitance and electroreflectance measurements in the semiconductor/electrolyte configuration. At lower values of the chemical potential, a monolayer of a sulphur surface compound is formed by replacement of phosphorus atoms. For higher values of the chemical potential a three-dimensional growth occurs, the layer is composed of In2S2 with little amounts of In2S 3. The main effect of sulphidation is to reduce the barrier height of the electrolytic junctions, by bringing the InP near-surface region into the accumulation mode.La sulfuration du phosphure d'indium de type N, faiblement dopé (N D ~ 1016 cm-3), dans une atmosphère réactive de H2S/H2 à 280 °C est étudiée. Les modifications superficielles sont caractérisées à l'aide de plusieurs techniques d'analyse de surface, AES, RHEED et par radiotraceur du soufre 35. Les caractéristiques électriques sont ensuite étudiées par mesures de capacité et d'électroréflexion en milieu électrolytique. On observe la formation d'une monocouche de sulfure avec remplacement du phosphore aux faibles pressions partielles de H2S. Pour les pressions plus élevées apparaît la croissance tridimensionnelle d'un composé du type In2S2 contenant probablement de l'In 2S3. La sulfuration provoque une diminution de la hauteur de barrière des jonctions InP/électrolyte due à la mise en régime d'accumulation du semiconducteur en surface

Characterization of a neocentric supernumerary marker chromosome originating from the Xp distal region by FISH, CENP-C staining, and array CGH

A small supernumerary marker chromosome (SMC) was observed in a girl with severe developmental delay. Her dysmorphism included prominent forehead, hypertelorism, down-slanting palpebral fissures, low-set/large ears, and flat nasal bridge with anteverted nares. This case also presented hypotonia, hypermobility of joints, congenital heart defect, umbilical hernia, failure to thrive, and seizures. The SMC originated from the distal region of Xp as identified by FISH with multiple DNA probes. Staining with antibodies to Centromere Protein C (CENP-C) demonstrated a neocentromere, while FISH with an α-satellite DNA probe showed no hybridization to the SMC. A karyotype was described as 47,XX,+neo(X)(pter→p22.31::p22.31→pter), indicating a partial tetrasomy of Xp22.31→pter. This karyotype represents a functional trisomy for Xp22.31→pter and a functional tetrasomy for the pseudoautosomal region given that there is no X-inactivation center in the marker chromosome. The SMC was further characterized by microarray-based comparative genomic hybridization (array CGH) as a duplicated DNA fragment of approximately 13 megabase pairs containing about 100 genes. We have described here a new neocentromere with discussion of its clinical significance