Lena Tjeldhorn - Academia.edu (original) (raw)

Papers by Lena Tjeldhorn

Research paper thumbnail of Search for correlations betweenFBN1 genotype and complete Ghent phenotype in 44 unrelated Norwegian patients with Marfan syndrome

American Journal of …, 2007

In monogenic disorders, correlation between genotype and phenotype is a premise for predicting pr... more In monogenic disorders, correlation between genotype and phenotype is a premise for predicting prognosis in affected patients. Predictive genetic testing may enable prophylaxis and promote clinical follow-up. Although Marfan syndrome (MFS) is known as a ...

Research paper thumbnail of Hereditary protein C deficiency caused by the Ala267Thr mutation in the protein C gene is associated with symptomatic and asymptomatic venous thrombosis

Thrombosis Research - THROMB RES, 2010

IntroductionProtein C (PC) is a key anticoagulant that regulates hemostasis, and inherited defici... more IntroductionProtein C (PC) is a key anticoagulant that regulates hemostasis, and inherited deficiency of PC is an established risk factor for venous thrombosis (VT). The factor V Leiden mutation causing activated PC (APC) resistance is an additional risk factor for VT. Reduced PC levels in the circulation and/or APC resistance do not necessarily lead to thrombotic disease. In the present study we describe and characterize an ethnic Lebanese family in which individuals with reduced PC levels and APC resistance have various clinical symptoms.

Research paper thumbnail of Qualitative and quantitative analysis of FBN1 mRNA from 16 patients with Marfan Syndrome

BMC Medical Genetics, 2015

Pathogenic mutations in FBN1, encoding the glycoprotein, fibrillin-1, cause Marfan syndrome (MFS)... more Pathogenic mutations in FBN1, encoding the glycoprotein, fibrillin-1, cause Marfan syndrome (MFS) and related connective tissue disorders. In the present study, qualitative and quantitative effects of 16 mutations, identified in FBN1 in MFS patients with systematically described phenotypes, were investigated in vitro. Qualitative analysis was performed with reverse transcription-PCR (RT-PCR) and gel electrophoresis, and quantitative analysis to determine the FBN1 mRNA levels in fibroblasts from the 16 patients with MFS was performed with real-time PCR. Qualitative analysis documented that the mutations c.4817-2delA and c.A4925G led to aberrant FBN1 mRNA splicing leading to in frame deletion of exon 39 and in exon 39, respectively. No difference in the mean FBN1 mRNA level was observed between the entire group of cases and controls, nor between the group of patients with missense mutations and controls. The mean expression levels associated with premature termination codon (PTC) and ...

Research paper thumbnail of Protein C Mutation (A267T) Results in ER Retention and Unfolded Protein Response Activation

PloS one, 2011

Background: Protein C (PC) deficiency is associated with a high risk of venous thrombosis. Recent... more Background: Protein C (PC) deficiency is associated with a high risk of venous thrombosis. Recently, we identified the PC-A267T mutation in a patient with PC deficiency and revealed by in vitro studies decreased intracellular and secreted levels of the mutant. The aim of the present study was to characterize the underlying mechanism(s).

Research paper thumbnail of Prevalence data on all Ghent features in a cross-sectional study of 87 adults with proven Marfan syndrome

European Journal of Human Genetics, 2009

The prevalence of each single feature in the Ghent criteria in patients with Marfan syndrome (MFS... more The prevalence of each single feature in the Ghent criteria in patients with Marfan syndrome (MFS) is not known. To elucidate this, a cross-sectional study of 105 adults with presumed MFS was carried out. All patients were examined by the same group of investigators with standardized and complete assessment of all features in the Ghent criteria. Eighty-seven (83%) fulfilled the criteria in 56 different variants. The most prevalent major criterion in Ghent-positive persons was dural ectasia (91%), followed by major genetic criterion (89%) and ectopic lenses (62 %). In 14 persons (16%), the diagnosis was dependent on the dural findings. In all, 79% fulfilled both major dural and major genetic (positive family history and/or FBN1 mutation) criteria, suggesting that most patients with MFS might be identified by investigating these criteria. A history or finding of ascending aortic disease was present in 46 patients (53%). This low prevalence might partly reflect a high number of diagnosed patients encompassing the whole spectrum of the syndrome. The study confirms the need to examine for the complete set of features in the Ghent criteria to identify all patients with MFS. The majority of persons with MFS might be identified by the combined assessment of dura mater and family history, supplemented with DNA analysis in familynegative cases. The low prevalence of ascending aortic disease might indicate better future prospects in an adult population than those traditionally considered.

Research paper thumbnail of Search for correlations betweenFBN1 genotype and complete Ghent phenotype in 44 unrelated Norwegian patients with Marfan syndrome

American Journal of …, 2007

In monogenic disorders, correlation between genotype and phenotype is a premise for predicting pr... more In monogenic disorders, correlation between genotype and phenotype is a premise for predicting prognosis in affected patients. Predictive genetic testing may enable prophylaxis and promote clinical follow-up. Although Marfan syndrome (MFS) is known as a ...

Research paper thumbnail of Hereditary protein C deficiency caused by the Ala267Thr mutation in the protein C gene is associated with symptomatic and asymptomatic venous thrombosis

Thrombosis Research - THROMB RES, 2010

IntroductionProtein C (PC) is a key anticoagulant that regulates hemostasis, and inherited defici... more IntroductionProtein C (PC) is a key anticoagulant that regulates hemostasis, and inherited deficiency of PC is an established risk factor for venous thrombosis (VT). The factor V Leiden mutation causing activated PC (APC) resistance is an additional risk factor for VT. Reduced PC levels in the circulation and/or APC resistance do not necessarily lead to thrombotic disease. In the present study we describe and characterize an ethnic Lebanese family in which individuals with reduced PC levels and APC resistance have various clinical symptoms.

Research paper thumbnail of Qualitative and quantitative analysis of FBN1 mRNA from 16 patients with Marfan Syndrome

BMC Medical Genetics, 2015

Pathogenic mutations in FBN1, encoding the glycoprotein, fibrillin-1, cause Marfan syndrome (MFS)... more Pathogenic mutations in FBN1, encoding the glycoprotein, fibrillin-1, cause Marfan syndrome (MFS) and related connective tissue disorders. In the present study, qualitative and quantitative effects of 16 mutations, identified in FBN1 in MFS patients with systematically described phenotypes, were investigated in vitro. Qualitative analysis was performed with reverse transcription-PCR (RT-PCR) and gel electrophoresis, and quantitative analysis to determine the FBN1 mRNA levels in fibroblasts from the 16 patients with MFS was performed with real-time PCR. Qualitative analysis documented that the mutations c.4817-2delA and c.A4925G led to aberrant FBN1 mRNA splicing leading to in frame deletion of exon 39 and in exon 39, respectively. No difference in the mean FBN1 mRNA level was observed between the entire group of cases and controls, nor between the group of patients with missense mutations and controls. The mean expression levels associated with premature termination codon (PTC) and ...

Research paper thumbnail of Protein C Mutation (A267T) Results in ER Retention and Unfolded Protein Response Activation

PloS one, 2011

Background: Protein C (PC) deficiency is associated with a high risk of venous thrombosis. Recent... more Background: Protein C (PC) deficiency is associated with a high risk of venous thrombosis. Recently, we identified the PC-A267T mutation in a patient with PC deficiency and revealed by in vitro studies decreased intracellular and secreted levels of the mutant. The aim of the present study was to characterize the underlying mechanism(s).

Research paper thumbnail of Prevalence data on all Ghent features in a cross-sectional study of 87 adults with proven Marfan syndrome

European Journal of Human Genetics, 2009

The prevalence of each single feature in the Ghent criteria in patients with Marfan syndrome (MFS... more The prevalence of each single feature in the Ghent criteria in patients with Marfan syndrome (MFS) is not known. To elucidate this, a cross-sectional study of 105 adults with presumed MFS was carried out. All patients were examined by the same group of investigators with standardized and complete assessment of all features in the Ghent criteria. Eighty-seven (83%) fulfilled the criteria in 56 different variants. The most prevalent major criterion in Ghent-positive persons was dural ectasia (91%), followed by major genetic criterion (89%) and ectopic lenses (62 %). In 14 persons (16%), the diagnosis was dependent on the dural findings. In all, 79% fulfilled both major dural and major genetic (positive family history and/or FBN1 mutation) criteria, suggesting that most patients with MFS might be identified by investigating these criteria. A history or finding of ascending aortic disease was present in 46 patients (53%). This low prevalence might partly reflect a high number of diagnosed patients encompassing the whole spectrum of the syndrome. The study confirms the need to examine for the complete set of features in the Ghent criteria to identify all patients with MFS. The majority of persons with MFS might be identified by the combined assessment of dura mater and family history, supplemented with DNA analysis in familynegative cases. The low prevalence of ascending aortic disease might indicate better future prospects in an adult population than those traditionally considered.