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De 1821 à 1883, le domaine de Chambord a appartenu à Henri, duc de Bordeaux puis comte de Chambord, petit-fils du roi Charles X et héritier du trône de France. À sa mort ses neveux, les princes de Bourbon-Parme, ont hérité du domaine et l’ont géré jusqu’à la mise sous séquestre en 1915. Les quelques salles du château ouvertes au public depuis 1821 ne présentent que peu d’œuvres ou d’objets d’art, tout le mobilier ayant été vendu à la Révolution. Mais à partir des années 1848-1850, une politique d’acquisition est mise en œuvre par le prince en exil grâce à son administration sur place. Eloigné de ses partisans, il se veut proche des Français et cherche à faire du château un lieu de mémoire dynastique des Bourbons, faute de restauration monarchique. Une étude systématique des archives du domaine déposées aux Archives départementales de Loir-et-Cher permet de comprendre le parti pris pour ces aménagements de salles et ces achats d’œuvres d’art. Sur une plus longue durée, il faut aussi mettre en perspective les choix de présentation faits depuis 1930, date d’acquisition du domaine par l’État pour en analyser l’histoire diachronique. From 1821 to 1883, the Chambord estates belonged to Henri, Duke of Bordeaux, the Count of Chambord who was the grandson of King Charles X and pretender to the throne of France. At his death, his nephews, the princes of Bourbon-Parme family, inherited the estate and managed it until its sequestration in 1915.The handful of rooms in the château that were opened to the public from 1821 presented only a few objects and works of art, the furniture having been sold of during the Revolution. But from the years 1848-1850 onwards, the Duke of Bordeaux, then in exile, launched a programme of acquisition, undertaken by his administrative services. Far from his partisans, he wished to remain close to the French people and attempted to make of the château a place of dynastic memory for the Bourbon framily, in anticipation of the restoration of the monarchy. The systematic strudy of the estate’s archives, held by the Loir-et-Cher departmental archives, allows for a better understanding of how the rooms were to be organised and how works of art were purchansed according to these plans. From a longer term point of view, for a proper diachronic analysis, it is also necessary to take into account the presentation choices made after 1930 when the estate was acquired by the French State.

Background: Among the well characterized X-linked conditions causing mental retardation, mutations in the methyl-CpG-binding protein 2 gene (MECP2) in Xq28 have been found in up to 85% of patients with Rett syndrome, a neurologic disorder which, in addition to other symptoms, severely affects higher cognitive functions in females. Mutations in the MECP2 gene are involved in a broad spectrum of phenotypes from classical Rett syndrome to mild intellectual difficulties in females and neonatal encephalopathy in males. Recently, mutations in the MECP2 gene were reported in males with non-specific mental retardation suggesting that defects in MECP2 could be responsible for up to 2% of X-linked mental retardation. Methods: We screened by denaturing high-pressure liquid chromatography the entire coding region and flanking intronic sequences of the MECP2 gene in a cohort of 354 mentally retarded males found negative for an expansion across the FRAXA CGG repeat and in a family in which a boy and his sister were mentally retarded. Results: We identified mainly silent polymorphisms within the MECP2 gene, together with four sequence alterations of unknown significance, i.e. three missense mutations (T197M, T228S, and P376S) and one substitution at position −19 in intron 3 (378-19delT). Further familial investigations allowed us to ruled out a pathogenic effect for the intronic variant, the T228S and the P376S missense mutations. Conclusions: These results confirm that MECP2 mutations in males are far more rare than initially thought and call for a careful evaluation of the pathogenicity of the MECP2 missense mutations identified in mentally retarded males before genetic counseling is proposed to the relatives.

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene have been found to be a cause of Rett syndrome (RTT). Mutation screening was based on various techniques including denaturing gradient gel electrophoresis, single-strand conformation polymorphism analysis, heteroduplex analysis, DNA sequencing and recently Southern Blot analysis. Mutation detection was achieved in 80% of typical RTT with a high prevalence of recurrent mutations. In order to provide further insights into the spectrum of MECP2 rearrangements in patients without any point mutation or small deletion/insertion in the coding region MECP2 gene, we screened 25 classical RTT females using fluorescence in situ hybridization analysis. No deletion were found in our group, suggesting that MECP2 gross rearrangements are a rare cause of Rett syndrome.

Acute promyelocytic leukaemia (APL) exhibits a characteristic t(15;17) translocation that fuses the PML gene on 15q22 to the retinoic acid receptor [alpha] (RARA) gene on 17q12-q21.1. In a small subset of acute promyelocytic-like leukaemias (APL-L), RARA is fused to a different partner: PLZF, NPM or NuMA. We report on the molecular characterization of a RARA gene rearrangement in a patient with an APL-L associated with a der(17). Thanks to the 5' RACE PCR approach, we demonstrate that the Signal Transducer and Activator of Transcription STAT5b gene is fused to RARA; STAT5b belongs to a family of latent cytosolic transcription factors activated by JAK tyrosine kinases., Les leucémies aiguës promyélocytaires (LAP) sont caractérisées par une signature chromosomique, la translocation t(15;17) résultant en un gène de fusion associant PML au gène codant le récepteur [alpha] de l'acide rétinoïque (RARA). Dans de rares cas de LAP atypiques (LAP-L), RARA est fusionné à différents partenaires : PLZF, NPM et NuMA. Au cours de ce travail, nous avons réalisé l'étude moléculaire d'un der(17) associé à une LAP-L. Par la technique de 5' RACE PCR, nous avons identifié un cinquième partenaire de RARA, STAT5b qui appartient à la famille des facteurs de transcription cytosoliques (Signal Transducer and Activator of Transcription) activés par les tyrosine kinases JAK. [...]

Acute promyelocytic leukaemia (APL) exhibits a characteristic t(15;17) translocation that fuses the PML gene on 15q22 to the retinoic acid receptor [alpha] (RARA) gene on 17q12-q21.1. In a small subset of acute promyelocytic-like leukaemias (APL-L), RARA is fused to a different partner: PLZF, NPM or NuMA. We report on the molecular characterization of a RARA gene rearrangement in a patient with an APL-L associated with a der(17). Thanks to the 5' RACE PCR approach, we demonstrate that the Signal Transducer and Activator of Transcription STAT5b gene is fused to RARA; STAT5b belongs to a family of latent cytosolic transcription factors activated by JAK tyrosine kinases., Les leucémies aiguës promyélocytaires (LAP) sont caractérisées par une signature chromosomique, la translocation t(15;17) résultant en un gène de fusion associant PML au gène codant le récepteur [alpha] de l'acide rétinoïque (RARA). Dans de rares cas de LAP atypiques (LAP-L), RARA est fusionné à différents partenaires : PLZF, NPM et NuMA. Au cours de ce travail, nous avons réalisé l'étude moléculaire d'un der(17) associé à une LAP-L. Par la technique de 5' RACE PCR, nous avons identifié un cinquième partenaire de RARA, STAT5b qui appartient à la famille des facteurs de transcription cytosoliques (Signal Transducer and Activator of Transcription) activés par les tyrosine kinases JAK. [...]