Record RF performance of standard 90 nm CMOS technology

We have optimized 3 key RF devices realized in standard logic 90 nm CMOS technology and report a record performance in terms of n-MOS maximum oscillation frequency f/sub max/ (280 GHz), varactor tuning range and varactor and inductor quality factor

Ventricular noncompaction in a female patient with nephropathic cystinosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report an unusual and interesting case of a 24-year-old woman with nephropathic cystinosis in association with concomitant isolated noncompaction of the left ventricle. Left ventricular noncompaction usually presents with reduced exercise tolerance as a consequence of ventricular dysfunction, the result of embolus or with palpitations and syncope due to arrhythmia. There is no specific treatment directed at isolated noncompaction. Treatment is focused on the cause of presentation, with medication aimed at improving ventricular dysfunction, as well as treating and preventing thrombosis and arrhythmia.</p> <p>Case presentation</p> <p>Our patient presented with an episode of decompensated heart failure. Trans-thoracic echocardiography demonstrated excessive trabeculation with inter-trabecular recesses in the left ventricle typical of noncompaction of the left ventricle. The patient's admission was complicated by a cardiac arrest precipitated by ventricular tachycardia for which she subsequently underwent implantation of an automatic implantable cardioverter defibrillator.</p> <p>Conclusion</p> <p>This is, as far as we know, the first case report of the co-existence of nephropathic cystinosis and isolated noncompaction of the left ventricle. It highlights the importance of being vigilant to the diagnosis of left ventricular noncompaction.</p

Noncompaction of the Ventricular Myocardium Is Associated with a De Novo Mutation in the β-Myosin Heavy Chain Gene

Noncompaction of the ventricular myocardium (NVM) is the morphological hallmark of a rare familial or sporadic unclassified heart disease of heterogeneous origin. NVM results presumably from a congenital developmental error and has been traced back to single point mutations in various genes. The objective of this study was to determine the underlying genetic defect in a large German family suffering from NVM. Twenty four family members were clinically assessed using advanced imaging techniques. For molecular characterization, a genome-wide linkage analysis was undertaken and the disease locus was mapped to chromosome 14ptel-14q12. Subsequently, two genes of the disease interval, MYH6 and MYH7 (encoding the α- and β-myosin heavy chain, respectively) were sequenced, leading to the identification of a previously unknown de novo missense mutation, c.842G>C, in the gene MYH7. The mutation affects a highly conserved amino acid in the myosin subfragment-1 (R281T). In silico simulations suggest that the mutation R281T prevents the formation of a salt bridge between residues R281 and D325, thereby destabilizing the myosin head. The mutation was exclusively present in morphologically affected family members. A few members of the family displayed NVM in combination with other heart defects, such as dislocation of the tricuspid valve (Ebstein's anomaly, EA) and atrial septal defect (ASD). A high degree of clinical variability was observed, ranging from the absence of symptoms in childhood to cardiac death in the third decade of life. The data presented in this report provide first evidence that a mutation in a sarcomeric protein can cause noncompaction of the ventricular myocardium

Isolated noncompaction of the left ventricular myocardium in the adult is an autosomal dominant disorder in the majority of patients

Isolated noncompaction of the ventricular myocardium (INVM, MIM 300183 and 604169) is a congenital unclassified cardiomyopathy with numerous prominent trabeculations and deep intertrabecular recesses in a hypertrophied and hypokinetic myocardium. Mutations in the G4.5 gene result in a wide spectrum of severe infantile X-linked cardiomyopathic phenotypes including Barth syndrome with dilated cardiomyopathy and INVM. Molecular genetic analysis of INVM has only been performed in pediatric patients. Although adult INVM patients show similar cardiac abnormalities, the influence of genetic factors, especially of mutations in G4.5, is unknown. We analyzed 25 adult INVM patients for the presence of mutations in the G4.5 gene and performed a pedigree analysis of probands. Mutations were not found in the coding sequence or splice sites of G4.5. Systematic analysis of relatives from seven of nine probands showed multiple affected members consistent with an autosomal dominant pattern of inheritance in the majority of cases. We conclude that INVM in the adult is an autosomal dominant disorder rarely caused by mutations in G4.5 and therefore genetically distinct from infantile X-linked cases

Novel gene locus for autosomal dominant left ventricular noncompaction maps to chromosome 11p15

Background - Left ventricular noncompaction (LVNC) is a congenital unclassified cardiomyopathy with numerous prominent trabeculations and deep intertrabecular recesses in a hypertrophied and hypokinetic myocardium. It has been reported to occur in isolation or in association with congenital heart disease. Mutations in the X-linked G4.5 gene are responsible for cases of isolated LVNC in male infants, but G4.5 mutations were not found in patients with clinical onset of disease in adulthood. In addition, several families with LVNC and an autosomal dominant pattern of inheritance suggest genetic heterogeneity. Methods and Results - We performed a genome-wide linkage analysis in a family with autosomal dominant LVNC and show that a locus containing the LVNC disease gene maps to chromosome 11p15. A peak 2-point logarithm of odds score of 5.06 was obtained with marker D11S902 at θ=0. Haplotype analysis defined a critical interval of 6.4 centimorgan between D11S1794 and D11S928 corresponding to a physical distance of 6.8 megabases. No disease-causing mutation was identified in 2 prime positional candidate genes, muscle LIM protein (MLP) and SOX6. Conclusions - We have mapped a locus for autosomal dominant LVNC to a 6.8-megabase region on human chromosome 11p15. Identification of the disease gene will allow genetic screening and provide fundamental insight into the understanding of myocardial morphogenesis

Mutant Desmocollin-2 Causes Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous heart-muscle disorder characterized by progressive fibrofatty replacement of right ventricular myocardium and an increased risk of sudden cardiac death. Mutations in desmosomal proteins that cause ARVC have been previously described; therefore, we investigated 88 unrelated patients with the disorder for mutations in human desmosomal cadherin desmocollin-2 (DSC2). We identified a heterozygous splice-acceptor–site mutation in intron 5 (c.631-2A→G) of the DSC2 gene, which led to the use of a cryptic splice-acceptor site and the creation of a downstream premature termination codon. Quantitative analysis of cardiac DSC2 expression in patient specimens revealed a marked reduction in the abundance of the mutant transcript. Morpholino knockdown in zebrafish embryos revealed a requirement for dsc2 in the establishment of the normal myocardial structure and function, with reduced desmosomal plaque area, loss of the desmosome extracellular electron-dense midlines, and associated myocardial contractility defects. These data identify DSC2 mutations as a cause of ARVC in humans and demonstrate that physiologic levels of DSC2 are crucial for normal cardiac desmosome formation, early cardiac morphogenesis, and cardiac function

Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations