Cardiac myxomas are benign mesenchymal tumors that can present as components of the human autosomal dominant disorder Carney complex. Syndromic cardiac myxomas are associated with spotty pigmentation of the skin and endocrinopathy. Our linkage analysis mapped a Carney complex gene defect to chromosome 17q24. We now demonstrate that the PRKAR1α gene encoding the R1α regulatory subunit of cAMP-dependent protein kinase A (PKA) maps to this chromosome 17q24 locus. Furthermore, we show that PRKAR1α frameshift mutations in three unrelated families result in haploinsufficiency of R1α and cause Carney complex. We did not detect any truncated R1α protein encoded by mutant PRKAR1α. Although cardiac tumorigenesis may require a second somatic mutation, DNA and protein analyses of an atrial myxoma resected from a Carney complex patient with a PRKAR1α deletion revealed that the myxoma cells retain both the wild-type and the mutant PRKAR1α alleles and that wildtype R1α protein is stably expressed. However, in this atrial myxoma, we did observe a reversal of the ratio of R1α to R2β regulatory subunit protein, which may contribute to tumorigenesis. Further investigation will elucidate the cellspecific effects of PRKAR1α haploinsufficiency on PKA activity and the role of PKA in cardiac growth and differentiation.

The ultimate identification and analysis of the Carney complex disease gene at this human chromosome 17q2 locus will facilitate diagnosis and treatment of cardiac myxomas and will foster new concepts in regulation of cardiac cell growth and differentiation.

FAA disease is genetically heterogeneous. We have identified a novel FAA locus at chromosome 11q23.3-q24, a critical step toward elucidating 1 gene defect responsible for aortic dilatation. Future characterization of the FAA1 gene will enhance our ability to achieve presymptomatic diagnosis of aortic aneurysms and will define molecular mechanisms to target therapeutics.

While our work was in preparation for submission, we were apprised of the fact that Stratakis et al. had independently reached a similar conclusion regarding the identification of mutations in the gene encoding PRKAR1α in patients with Carney complex. These findings were subsequently published in

We describe an individual in whom molecular genetic testing provided a diagnosis of the Carney complex, an autosomal dominant syndrome comprising cutaneous and cardiac myxomas, spotty pigmentation of the skin, and endocrinopathy. Recently, we localized the Carney complex disease gene to chromosome region 17q2. Our patient was a member of a family segregating the Carney complex, but was not, himself, initially thought to be affected. Haplotype analysis based on genotyping studies with 17q2 microsatellites predicted that this individual was, in fact, affected by Carney complex and was at risk for development of myxomas. Further clinical evaluation and re-review of prior pathologic studies, then, confirmed the DNA-based diagnosis. This report highlights the difficulty in establishing a diagnosis of Carney complex based on clinical and pathologic findings alone, and we suggest that molecular genetic analyses provide an important diagnostic method for this familial myxoma syndrome.

Cardiac lipomas occur infrequently but account for a significant portion of rare cardiac tumors. Common cutaneous lipomas have previously been associated with rearrangements of chromosome band 12q15, which often disrupt the high‐mobility‐group protein gene HMGIC. In this report, we describe the cytogenetic analysis of an unusual giant cardiac lipoma that exhibited myocardial invasion in a patient with a history of multiple lipomatosis (cutaneous lipoma, lipomatous gynecomastia, lipomatous hypertrophy of the interatrial septum, and dyslipidemia). Cytogenetic studies of cells derived from the cardiac lipoma demonstrated no abnormalities of chromosome 12, but did reveal a t(2;19)(p13;p13.2). A liposarcoma‐derived oncogene (p115‐RhoGEF) previously mapped to chromosome 19 and the low‐density lipoprotein receptor gene (LDLR) previously mapped to chromosome band 19p13 were evaluated to determine whether they were disrupted by this translocation. Fluorescence in situ hybridization analyses assigned p115‐RhoGEF to chromosome 19 in bands q13.2–q13.3 and mapped the LDLR to chromosome arm 19p in segment 13.2, but centromeric to the t(2;19) breakpoint. Thus, these genes are unlikely to be involved in the t(2;19)(p13;p13.2). Further studies of the regions of chromosomes 2 and 19 perturbed by the translocation in this unusual infiltrating cardiac lipoma will identify gene(s) that participate in adipocyte growth and differentiation and may provide insight into syndromes of multiple lipomatosis. Genes Chromosomes Cancer 28:133–137, 2000. © 2000 Wiley‐Liss, Inc.

EDS is highly significant in the surgical context, with the causative genetic factors serving to further complicate the course of surgical intervention. In the absence of consensus regarding best surgical management, due consideration should be given to non-operative management of benign colonic perforation.

There is considerable debate about the choice of intravenous platelet glycoprotein IIb/IIIa inhibitors for percutaneous coronary intervention, after a meta-analysis of 7 trials and 16,770 patients has shown a 38% reduction in death or non-fatal MI 30 days after the index procedure. At 149 hospitals in 18 countries throughout North America, Europe and Australia, 4810 patients were randomized between 12/30/99 and 8/25/00 and treated with either tirofiban or abciximab on a double-blind, double dummy basis. Clopidogrel and aspirin were administered preprocedurally, along with a 70 U/kg intravenous heparin bolus. The dose of tirofiban was 10 mcg/kg bolus and 0.15 mcg/kg/min infusion for 18 -24 hrs; for abciximab it was 0.25 mcg/kg bolus and 0.125 mcg/kg/min (max 10 mcg/min) infusion. Patients qualified by having suitable anatomy for "intent-to-stent" lesions addressed by percutaneous revascularization, and were not with evolving ST-elevation MI or with serum creatinine Ͼ2.5 mg/dl. The primary endpoint is 30 death or non-fatal MI and the trial has Ͼ80% power to determine non-inferiority for tirofiban with an expected event rate in the control (abciximab) group of 5.3% based on the EPISTENT trial. The primary endpoint data will be presented along with the key subgroups such as diabetics. Follow-up data for the trial to 1 year will also be performed. Late Breaking Science: Linking Genes to Function in the Heart and Vasculature BASIC ABSTRACTS Exogenous Hematopoietic Stem Cells Can Regenerate Infarcted MyocardiumDonald Orlic, Jan Kajstura, Stefano Chimenti, Baosheng Li, Stacie Anderson, David Bodine, James Pickel, Annarosa Leri, Bernardo Nadal-Ginard, Piero Anversa, New York Medical College, Valhalla, NY; NHGRI/NIH, Bethesda, MD To determine whether hematopoietic stem cells (HSC) can transform into cardiomyocytes with the potential to repair dead myocardium after infarction, Lin/c-kit I-II HSC were harvested from transgenic mice expressing green fluorescent protein (GFP) and injected in the region bordering the infarct, 3-5 hours after coronary artery occlusion in mice. A band of closely packed cells was identified 7 to 17 days later in nearly 50% of HSC injected hearts, between the endocardial and epicardial surface of the infarcted ventricle. This band occupied 50 75% of the damaged portion of the wall. c-kit/GFP positive HSC were found in the infarcted area shortly after coronary ligation and were still detectable at 7 days. c-kit stained HSC were not labeled by markers of myocytes, ␣-sarcomeric actin and myosin, endothelial cells, factor VIII, and smooth muscle cells, smooth muscle actin. The band of tissue included in the infarcted zone was constituted 75% by GFP, ␣-sarcomeric actin, myosin and ␣-actinin positive cardiac muscle cells. Other GFP-positive cell populations were endothelial cells and smooth muscle cells, organized in nascent capillary structures and arterioles. Proliferating myocytes were small with partially aligned myofibrils and resembled late fetal-neonatal cells. GFP-positive replicating myocytes, ...