Despite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs.

If quality begets customer satisfaction and customer satisfaction begets customer retention, why doesn't customer retention beget customer loyalty—and greater profits? Because loyalty's a fickle thing—and needs proper management to thrive.

Cutaneous T cell lymphomas are a rare subset of non-Hodgkin’s lymphomas with predilection for the skin with immunosuppressive effects that drive morbidity and mortality. We are now appreciating that suppression of the immune system is an important step in the progression of disease. It should come as no surprise that therapies historically and currently being used to treat these cancers have immune modulating functions that impact disease outcomes. By understanding the immune effects of our therapies, we may better develop new agents that target the immune system and improve combinatorial treatment strategies to limit morbidity and mortality of these cancers. The immune modulating effect of therapeutic drugs in use and under development for cutaneous T cell lymphomas will be reviewed.