A form of the metabolic syndrome associated with mutations in DYRK1B.

BACKGROUND: Genetic analysis has been successful in identifying causative mutations for individual cardiovascular risk factors. Success has been more limited in mapping susceptibility genes for clusters of cardiovascular risk traits, such as those in the metabolic syndrome. METHODS: We identified three large families with coinheritance of early-onset coronary artery disease, central obesity, hypertension, and diabetes. We used linkage analysis and whole-exome sequencing to identify the disease-causing gene. RESULTS: A founder mutation was identified in DYRK1B, substituting cysteine for arginine at position 102 in the highly conserved kinase-like domain. The mutation precisely cosegregated with the clinical syndrome in all the affected family members and was absent in unaffected family members and unrelated controls. Functional characterization of the disease gene revealed that nonmutant protein encoded by DYRK1B inhibits the SHH (sonic hedgehog) and Wnt signaling pathways and consequently enhances adipogenesis. Furthermore, DYRK1B promoted the expression of the key gluconeogenic enzyme glucose-6-phosphatase. The R102C allele showed gain-of-function activities by potentiating these effects. A second mutation, substituting proline for histidine 90, was found to cosegregate with a similar clinical syndrome in an ethnically distinct family. CONCLUSIONS: These findings indicate a role for DYRK1B in adipogenesis and glucose homeostasis and associate its altered function with an inherited form of the metabolic syndrome. (Funded by the National Institutes of Health.).

Rupture of a giant cardiac hydatid cyst in the left ventricular free wall: successful surgical management of a rare entity.

Hydatid cyst of heart is a rare but potentially fatal site of pathology, especially left ventricular free wall. We managed a successful surgical treatment on a case of a 24 year old man who had a giant cardiac hydatid cyst (71 x 64 mm) that ruptured left ventricular free wall. The cyst was excised gently and all the cystic materials were removed, the cyst cavity was closed with GORE-TEX soft tissue patch. The patient was discharged on the 9th postoperative day without symptoms. This case is different from other cardiac hydatid cysts that have been reported in literature previously; because this patient was young and had advanced phase of the disease that presented to our clinic lately. Additionally, the cyst had limited both ventricular volumes significantly.

Effect of staged preconditioning on biochemical markers in the patients undergoing coronary artery bypass grafting.

The present study has investigated the effectiveness of staged-preconditioning, in both remote and target organs. After IP the myocardial release of the biochemical markers including, creatine phosphokinase (CPK), cardiac creatine kinase (CK-MB), cardiac troponin T (cTnT) and lactate dehydrogenase (LDH) were evaluated in patients who underwent CABG, with and without staged-preconditioning. Sixty-one patients entered the study; there were 32 patients in the staged-preconditioning group and 29 patients in the control group. All patients underwent on-pump CABG using cardiopulmonary bypass (CPB) techniques. In the staged-preconditioning group, patients underwent two stages of IP on remote (upper limb) and target organs. Each stage of preconditioning was carried out by 3 cycles of ischemia and then reperfusion. Serum levels of biochemical markers were immediately measured postoperatively at 24, 48 and 72 h. Serum CK-MB, CPK and LDH levels were significantly lower in the staged-preconditioning group than in the control group. The CK-MB release in the staged-preconditioning patients reduced by 51% in comparison with controls over 72 h after CABG. These results suggest that myocardial injury was attenuated by the effect of three rounds of both remote and target organ IP.