Clinical characterization and mutation spectrum of patients with hypertriglyceridemia in a German outpatient clinic.

Background: Severe hypertriglyceridemia (HTG) has predominantly multifactorial causes (MCS). Yet a small subset of patients have the monogenetic form (FCS). It remains a challenge to distinguish patients clinically, since decompensated MCS might mimic FCS´s severity.

FH ALERT: efficacy of a novel approach to identify patients with familial hypercholesterolemia.

Diagnosis rates of familial hypercholesterolemia (FH) remain low. We implemented FH ALERT to assess whether alerting physicians for the possibility of FH impacted additional diagnostic activity. The study was conducted from SYNLAB laboratory Weiden (Bavaria).

Clinical characterization and mutation spectrum of German patients with familial hypercholesterolemia.

Background And Aims: Autosomal-dominant familial hypercholesterolemia (FH) is characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and a dramatically increased risk to develop cardiovascular disease (CVD). Mutations in three major genes have been associated with FH: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB), and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). Here we investigated the frequency and the spectrum of FH causing mutations in Germany.

Severe hypertriglyceridemia in a patient heterozygous for a lipoprotein lipase gene allele with two novel missense variants.

Rare monogenic hyperchylomicronemia is caused by loss-of-function mutations in genes involved in the catabolism of triglyceride-rich lipoproteins, including the lipoprotein lipase gene, LPL. Clinical hallmarks of this condition are eruptive xanthomas, recurrent pancreatitis and abdominal pain. Patients with LPL deficiency and severe or recurrent pancreatitis are eligible for the first gene therapy treatment approved by the European Union.

High-density oligonucleotide-based resequencing assay for mutations causing syndromic and non-syndromic forms of thoracic aortic aneurysms and dissections.

Thoracic aortic aneurysm and dissection is associated with increasing mortality rate that may occur as part of a syndrome or as an isolated familial condition. Several genes have been implicated in causing TAAD, though an appropriate genetic test for their parallel testing is not yet available. Herein, we describe the novel 117-kb "MFSTAAD chip" that may help to understand the genetic basis of TAAD.

Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure.

Aims: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding β-myosin heavy chain (MYH7) or cardiac myosin-binding protein C (MYBPC3). The aim of the present study was to determine the prevalence and spectrum of mutations in both genes in German HCM and DCM patients and to establish novel genotype-to-phenotype correlations.

Methods And Results: Coding exons and intron flanks of the two genes MYH7 and MYBPC3 of 236 patients with HCM and 652 patients with DCM were sequenced by conventional and array-based means.

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry.

Background: Recent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI.

Three novel mutations in the ACTA2 gene in German patients with thoracic aortic aneurysms and dissections.

Mutations in the gene encoding smooth muscle cell alpha actin (ACTA2) have recently been shown to cause familial thoracic aortic aneurysms leading to type A dissections (TAAD) and predispose to premature stroke and coronary artery disease. In order to further explore the role of ACTA2 variations in the pathogenesis of TAAD, we sequenced the coding regions of this gene in 40 unrelated German patients with TAAD (with (n=21) or without (n=19) clinical features suggestive of Marfan syndrome). All patients had previously tested negative for mutations in the FBN1 and TGFBR2 genes.

Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention.

Background: Restenosis represents the major limiting factor for the long-term efficacy of percutaneous coronary intervention (PCI). Several genetic factors involved in the regulation of the vascular system have been described to play a role in the pathogenesis of restenosis. We investigated whether the EPHX2 K55R polymorphism, previously linked to significantly higher risk for coronary heart disease (CHD), was associated with the occurrence of restenosis after PCI.

Array-based resequencing assay for mutations causing hypertrophic cardiomyopathy.

Background: Dissecting the complex genetic basis of hypertrophic cardiomyopathy (HCM) may be key to both better understanding and optimally managing this most prevalent genetic cardiovascular disease. An array-based resequencing (ABR) assay was developed to facilitate genetic testing in HCM.

Methods: An Affymetrix resequencing array and a single long-range PCR protocol were developed to cover the 3 most commonly affected genes in HCM, MYH7 (myosin, heavy chain 7, cardiac muscle, beta), MYBPC3 (myosin binding protein C, cardiac), and TNNT2 [troponin T type 2 (cardiac)].

Noncompaction of the ventricular myocardium is associated with a de novo mutation in the beta-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.

[Hypertrophic cardiomyopathy].

Hypertrophic cardiomyopathy (HCM) counts as one of primary diseases emanating from the myocardium. In approximately 60% of the cases a familial autosomal dominant trait of disease inheritance was determined. In the majority of the cases a mutation in one of the known 14 disease-causing genes could be proven.

MHC class I antigen processing pathway defects, ras mutations and disease stage in colorectal carcinoma.

Colorectal tumorigenesis has been associated with the progressive acquisition of a variety of genetic alterations. These include mutations of the Ki-ras proto-oncogene in codons 12 and 13, which account for 85% of genetic changes in colorectal cancer. In murine in vitro models of oncogenic transformation, an association between ras-mediated transformation and downregulation of different components of the MHC class I antigen processing machinery (APM) has been described.

Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy.

Background: Muscle LIM protein (MLP) is an essential nuclear regulator of myogenic differentiation. Additionally, it may act as an integrator of protein assembly of the actin-based cytoskeleton. MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM).

Hox genes in the honey bee Apis mellifera.

Hox genes are known to control the identity of serially repeated structures in arthropods and vertebrates. We analyzed the expression pattern of the Hox genes Deformed (Dfd), Sex combs reduced (Scr), Antennapedia (Antp), and Ultrabithorax/abdominal-A (Ubx/abd-A) from the honey bee Apis mellifera. We also cloned a cDNA with the complete coding region of the Antennapedia gene from Apis.

An outcome study of Missouri's CSTAR alcohol and drug abuse programs.

The Comprehensive Substance Abuse Treatment and Rehabilitation (CSTAR) program is described, and a study of its services is presented. The CSTAR program is a community program with wrap-around services and intensive case management. Eleven domains typically affected by substance abuse were measured, plus satisfaction with treatment services.

Pair-rule patterning in the honeybee Apis mellifera: Expression of even-skipped combines traits known from beetles and fruitfly.

 We have studied the binding pattern of antibody mAB 2B8 directed against even-skipped orthologous proteins (EVE) in honeybee embryos. Primary and secondary EVE stripes form in roughly anterior-to-posterior succession; there are 8 primary and 16 secondary stripes. The most posterior primary stripes appear only after the onset of gastrulation.

Containing mental health treatment costs through program design: a Massachusetts study.

A single site pre-post study of seriously mentally ill patients treated in a public mental health system shows that annual treatment costs can be substantially reduced with the use of day hospital treatment. Two cohorts of psychiatric patients--282 consecutive admissions to a traditional public inpatient unit in 1980, and 340 consecutive admissions to a combination of inpatient and day hospital care in 1984--were followed 12 months after admission. The substitution of the day hospital is made possible because the facility provided a dormitory residence for those who could not go home at night.

Output value analysis of an alcoholism treatment program.

A form of cost--benefit analysis is used to measure the efficiency and effectiveness of an alcoholism treatment program in caring for patients grouped by year of admission, sex and level of impairment.

Predicting resource utilization in a comprehensive center: an evaluation of three alternative methods.

Three alternative methods for obtaining anticipated resource utilization information for comprehensive mental health centers are proposed. The methods differ on two dimensions, sample selection and statistical technique. Using an admission cohort rather than a discharge cohort and eliminating patients who terminated treatment against medical advice permitted a refined prediction.

Workload levels, program costs, and program benefits: an output value analysis.

This study analyzes the relationship between program performance and workload levels. The results indicate that program effectiveness is highest under medium workloads while efficiency is greatest under high workloads. The management dilemma resulting from these findings is discussed.

Readmission discount factors in program evaluation. An output value analysis of an adult psychiatry program.

The application of output value analysis, a type of benefit/cost analysis, to a psychiatric patient population is reported. A method for discounting the value of the program if a patient was readmitted within a year after discharge was introduced. The application of this discount factor reduces the value produced by the program and thereby reduces both productivity and effectiveness indices.