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Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France,(More)
Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease Aims The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of(More)
The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from(More)
The discovery of autosomal dominant hypercholesterolemic patients with mutations in the PCSK9 gene, encoding the proprotein convertase NARC-1, resulting in the missense mutations suggested a role in low density lipoprotein (LDL) metabolism. We show that the endoplasmic reticulum-localized proNARC-1 to NARC-1 zymogen conversion is Ca2+-independent and that(More)
BACKGROUND Vast sample sizes are often essential in the quest to disentangle the complex interplay of the genetic, lifestyle, environmental and social factors that determine the aetiology and progression of chronic diseases. The pooling of information between studies is therefore of central importance to contemporary bioscience. However, there are many(More)
BACKGROUND Severe osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined. METHODS All SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical(More)
The low-density lipoprotein receptor (LDLr) plays a pivotal role in cholesterol homeostasis. Mutations in the LDLr gene (LDLR), which is located on chromosome 19, cause familial hypercholesterolemia (FH), an autosomal dominant disorder characterized by severe hypercholesterolemia associated with premature coronary atherosclerosis. To date almost 300(More)
OBJECTIVE We have reported further heterogeneity in familial autosomal-dominant hypercholesterolemia (FH) related to mutation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene previously named neural apoptosis regulated convertase 1 (Narc-1). Our aim was to define the metabolic bases of this new form of hypercholesterolemia. METHODS AND(More)
AIMS Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of(More)
The Marfan syndrome (MFS) is a prominent member of heritable disorders of connective tissue with manifestations involving primarily the skeletal, ocular and cardiovascular systems but also and less systematically investigated the lung, skin and integument, and dura. Over the last two decades, a considerable amount of clinical, molecular and protein data had(More)