Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93-1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.

The letters of Dorothy Wadham, 1609-1618;

Mode of access: Internet.

Monumens de l'histoire de France, en estampes et dessins ...

The present 30 volumes seem to have remained with the Dukes of Leuchtenberg, until the ducal library was acquired for sale in 1935 by the dealers Ulrich Hoepli (Milan) and Braus-Riggenbach (Basel). The volumes are not complete, as leaves have been wholly or partly removed throughout; this is particularly evident in preliminary volumes 2 and 10 and volume 75. Prints and the relatively small number of drawings are mostly French, with some German, Dutch and English, and are mostly of the 17th or 18th centuries. They are mounted generally on rectos of leaves, often with hand-written captions. Large prints are occasionally bound in directly; these are often folded. The engraved general title page (bearing the date 1788) appears at the beginning of each volume; below the printed title a hand-written volume number and brief title describing the volume's contents usually appear. In many volumes the title leaf is followed by a hand-written contents leaf listing the section titles, which are also written individually throughout the volume on leaves with etched decorative frames. Sections are numbered continuously throughout the work as a whole. Numbering of the leaves, when present, appears in black ink within each volume at top center recto. Printmakers include B. & J. Audran, Francesco Bartolozzi, Abraham Bosse, Stefano della Bella, Jacques Callot, François Chéreau, Wenceslaus Hollar, Romeyn de Hooghe, Raymond La Fage, Sébastien Le Clerc, Pierre Lepautre, Claude Mellan, Bernard Picart, and Simon Thomassin. There are also early color prints by Gautier-Dagoty and Jean-Baptiste Morret.