Clinical and Genetic Evaluation of People with or at Risk of Hereditary ATTR Amyloidosis: An Expert Opinion and Consensus on Best Practice in Ireland and the UK.

Hereditary transthyretin-mediated amyloidosis (hATTR) is challenging to diagnose early owing to the heterogeneity of clinical presentation, which differs according to the TTR gene variant and its penetrance in each individual. The TTR variants seen most frequently in the UK and Ireland (T80A, V142I and V50M) differ to those commonly occurring in other geographic locations and warrant a specific consideration for diagnosis and genetic testing. In addition, recent availability of treatment for this condition has reinforced the need for a more consistent approach to the management of patients, including access to specialist services, genetic testing and counselling, and clinical investigation for families living in the UK and Ireland.

Characterization of a Dual CDC7/CDK9 Inhibitor in Multiple Myeloma Cellular Models.

Two key features of myeloma cells are the deregulation of the cell cycle and the dependency on the expression of the BCL2 family of anti-apoptotic proteins. The cell division cycle 7 (CDC7) is an essential S-phase kinase and emerging CDC7 inhibitors are effective in a variety of preclinical cancer models. These compounds also inhibit CDK9 which is relevant for MCL-1 expression.

The interleukin 1 gene cluster contains a major susceptibility locus for ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common and highly heritable inflammatory arthropathy. Although the gene HLA-B27 is almost essential for the inheritance of the condition, it alone is not sufficient to explain the pattern of familial recurrence of the disease. We have previously demonstrated suggestive linkage of AS to chromosome 2q13, a region containing the interleukin 1 (IL-1) family gene cluster, which includes several strong candidates for involvement in the disease.