Search

Most patients diagnosed with human immunodeficiency virus (HIV) infection now receive effective treatment. However, as the HIV-infected population gets older, manifestations of aging is starting to emerge 10-15 years earlier than in the general population, such as cardiovascular disease, osteoporosis, neurocognitive disorders, metabolic complications, and kidney and liver failure. Clinical studies suggest that the pathophysiology of this premature aging may be multifactorial. In addition to residual HIV infection, immune activation (leading to immunodeficiency) and some antiretrovirals might contribute to low-grade systemic inflammation that could drive tissue senescence and provoke degenerative and proliferative disorders. Management of these patients involves lifestyle modifications and switching from first-generation antiretrovirals towards less toxic drugs. Antiinflammatory treatment could be considered for at-risk patients.

Lamins A and C, encoded by the LMNA gene, are nuclear proteins expressed in all post-mitotic cells. Together with B-type lamins, they form a meshwork of proteins beneath the inner nuclear membrane, the lamina, in connection with the cytoskeleton. Lamins A/C also interact with chromatin and numerous proteins, including transcription factors. Mutations in LMNA are responsible for more than ten different disorders, commonly called "laminopathies". These diseases affect tissues in a specific (striated muscle, adipose tissue, peripheral nerve) or in a systemic manner (premature ageing syndromes). This wide spectrum of phenotypes is associated to a wide variety of mutations. This large clinical and genetic heterogeneity, unique to the LMNA gene, makes genotype-phenotype relations particularly difficult to establish. However, correlations have been obtained in several cases. Hence, LMNA mutations identified in premature ageing syndromes lead to the accumulation of immature proteins with a toxic effect for cells. Mutations in laminopathies of the adipose tissue mainly localize in the Ig-like domain of the proteins, potentially affecting the interaction with the SREBP-1 transcription factor. In laminopathies of the striated muscles, the mutations are spread throughout the gene. These mutations are thought to induce structural modifications of the proteins, thereby affecting their polymerization into nuclear lamina. Such defect would lead to a mechanical weakness of the nuclear lamina and of the cells, particularly in striated muscles continuously stretching. The exploration of pathophysiological mechanisms of LMNA mutations largely benefits from the numerous mouse models created, which have been widely used to analyze affected molecular pathways and to test putative therapeutic treatments., (Société de Biologie, 2011.)

Cockayne syndrome is a rare autosomal recessive progressive neurological disorder characterized by a nanism, a major cachexy, a characteristic facial appearance of premature ageing, a sun-sensitivity, a retinopathy, and a mental retardation. We report three observations of Cockayne syndrome. The diagnostic criteria, notably clinical, found in these patients are discussed in comparison to the literature.