Loss of Tsc1 in cerebellar Purkinje cells induces transcriptional and translation changes in FMRP target transcripts.

Tuberous sclerosis complex (TSC) is a genetic disorder that is associated with multiple neurological manifestations. Previously, we demonstrated that Tsc1 loss in cerebellar Purkinje cells (PCs) can cause altered social behavior in mice. Here, we performed detailed transcriptional and translational analyses of Tsc1-deficient PCs to understand the molecular alterations in these cells. We found that target transcripts of the Fragile X Mental Retardation Protein (FMRP) are reduced in mutant PCs with evidence of increased degradation. Surprisingly, we observed unchanged ribosomal binding for many of these genes using translating ribosome affinity purification. Finally, we found that multiple FMRP targets, including SHANK2, were reduced, suggesting that compensatory increases in ribosomal binding efficiency may be unable to overcome reduced transcript levels. These data further implicate dysfunction of FMRP and its targets in TSC and suggest that treatments aimed at restoring the function of these pathways may be beneficial.

A case of mesothelial/monocytic cardiac excrescence causing severe acute cardiopulmonary failure.

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a benign lesion composed of a haphazard mixture of mesothelial cells, histiocytes, and fibrin, often found incidentally during cardiac valve replacement. Its pathogenesis is controversial with some authors favoring an artifactually produced amalgam while others espoused a reactive phenomenon. Clinically, this entity is important because of potential misdiagnoses as malignancies. We report a case in a 65-year-old man with severe acute aortic regurgitation. A 2.0-cm mobile aortic valve vegetation was documented by transesophageal echocardiography prior to any cardiac instrumentation. At surgery, the lesion was immediately visualized together with free-floating vegetation in the left ventricular outflow tract. Routine and immunohistochemical examination showed a nodule composed of predominantly histiocytes and mesothelial cells, together with fibrin and scattered neutrophils. To our knowledge, this is the first reported case of a mesothelial/monocytic cardiac excrescence causing acute cardiopulmonary failure. The literature on MICE is reviewed with discussion of its etiology.