Publications by authors named "Ingrid Krapels"

Aim: In this article, we present two cases of severe fetal hemolytic anemia based on a beta-thalassaemia trait inherited from a single parent.

Results: These cases, presented at 20 and 28 weeks' gestation, necessitated intra-uterine blood transfusions. This occurrence is remarkable because it challenges the common assumption that beta-thalassaemia typically has no prenatal implications regarding fetal anemia.

View Article and Find Full Text PDF
Article Synopsis
  • Systemic immune-mediated diseases (SIDs) may contribute to dilated cardiomyopathy (DCM), and this study aimed to explore the genetic predispositions present in DCM patients with SIDs.
  • The research involved 183 DCM-SID patients, identifying a significantly higher prevalence of pathogenic genetic variants in these individuals compared to healthy controls and DCM patients without SIDs.
  • Findings suggest that about 17-20% of DCM patients with SIDs have pathogenic variants, particularly truncating variants like TTN, indicating the importance of genetic testing for understanding the causes of immune-related DCM.
View Article and Find Full Text PDF

While next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use and re-use of exome sequencing is still emerging. We revisited clinical exome data from 1300 IEI patients using an updated in silico IEI gene panel. Variants were classified and curated through expert review.

View Article and Find Full Text PDF
Article Synopsis
  • - This study examines the link between rare variants in the cullin-3 ubiquitin ligase (CUL3) gene and neurodevelopmental disorders (NDDs), gathering data from multiple centers to explore genetic mutations and their clinical impacts.
  • - Researchers identified 37 individuals with CUL3 variants, most of which result in loss-of-function (LoF), leading to intellectual disabilities and possibly autistic traits; specific mechanisms affecting protein stability were also investigated.
  • - The findings enhance the understanding of NDDs associated with CUL3 mutations, suggesting that LoF variants are the main cause, which could help inform future diagnostics and treatment strategies.
View Article and Find Full Text PDF
Article Synopsis
  • * A study identified 25 individuals with new variations in the MSL2 gene, who exhibited NDD symptoms such as developmental delays, coordination problems, and autism spectrum disorder, along with other health concerns.
  • * iPSCs from affected individuals showed reduced MSL2 levels and changes in gene expression, leading to the characterization of a new MSL2-related disorder with unique clinical markers and a specific DNA episignature for diagnosis.
View Article and Find Full Text PDF
Article Synopsis
  • The study evaluates the effectiveness of genetic testing in patients with idiopathic ventricular fibrillation (VF) to uncover potential genetic causes of their condition.
  • Among 419 patients, 379 underwent genetic testing, revealing that 15% had likely pathogenic variants, primarily linked to the DPP6 gene.
  • The results suggest the need for a dedicated gene panel for idiopathic VF patients due to the high occurrence of variants of uncertain significance, especially with broad panel testing.
View Article and Find Full Text PDF

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5-5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI.

View Article and Find Full Text PDF

Purpose: variants in (Cullin-3 ubiquitin ligase) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here we aimed to collect sporadic cases carrying rare variants in describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism.

Methods: Genetic data and detailed clinical records were collected via multi-center collaboration.

View Article and Find Full Text PDF
Article Synopsis
  • TTN truncating variants (TTNtv) are the leading genetic cause of dilated cardiomyopathy (DCM), and this study focuses on comparing left atrial (LA) function between patients with and without these variants.
  • Results show that patients with TTNtv have larger LA volumes and reduced LA strain compared to those without genetic variants, indicating more severe LA dysfunction in the TTNtv group.
  • Computational modeling reveals that both left ventricular (LV) and LA dysfunction contribute to the observed differences between the two groups, highlighting complex interactions in heart function for DCM patients.
View Article and Find Full Text PDF

It was previously suggested that increasing the number of genes on diagnostic gene panels could increase the genetic yield in patient with dilated cardiomyopathy (DCM). We explored the diagnostic and prognostic relevance of testing DCM patients with an expanded gene panel. The current study included 225 consecutive DCM patients who had no genetic diagnosis after a 48-gene cardiomyopathy-panel.

View Article and Find Full Text PDF

Dilated cardiomyopathy is a heterogeneous disease characterized by multiple genetic and environmental etiologies. The majority of patients are treated the same despite these differences. The cardiac transcriptome provides information on the patient's pathophysiology, which allows targeted therapy.

View Article and Find Full Text PDF

Background: Dilated cardiomyopathy (DCM) was considered a monogenetic disease that can be caused by over 60 genes. Evidence suggests that the combination of multiple pathogenic variants leads to greater disease severity and earlier onset. So far, not much is known about the prevalence and disease course of multiple pathogenic variants in patients with DCM.

View Article and Find Full Text PDF

Objective: We performed a 1-year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy-number-neutral Absence-of-Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non-causative QF-PCR result.

Methods: After invasive diagnostics, whole exome parent-offspring trio-sequencing with exome-wide CNV analysis was performed in pregnancies with fetal US anomalies and a non-causative QF-PCR result (WES-CNV). On request, additional SNV-analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV-analysis afterward) was performed simultaneously (WES-CNV/SNV) or as rapid SNV-re-analysis, following a normal CNV analysis.

View Article and Find Full Text PDF
Article Synopsis
  • Dutch MFS growth charts were developed to enhance care for children with Marfan syndrome, focusing specifically on the impact of FBN1 variant types on growth.
  • Data from 389 MFS individuals was analyzed, revealing that their height increase was less than that of MFS populations in the U.S., Korea, and France in comparison to their respective general populations.
  • FBN1 haploinsufficiency variants were linked to taller heights in both genders and lower BMI in females, indicating that genetic background and variant type significantly influence growth patterns in individuals with MFS.
View Article and Find Full Text PDF

Background: Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption.

Objectives: This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD.

Methods: Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD.

View Article and Find Full Text PDF

Purpose: Heterozygous pathogenic/likely pathogenic (P/LP) variants in the ACTA2 gene confer a high risk for thoracic aortic aneurysms and aortic dissections. This retrospective multicenter study elucidates the clinical outcome of ACTA2-related vasculopathies.

Methods: Index patients and relatives with a P/LP variant in ACTA2 were included.

View Article and Find Full Text PDF
Article Synopsis
  • Brugada syndrome (BrS) is a serious heart condition linked to sudden death in young adults, with few known genetic factors beyond the SCN5A gene.
  • A large study involving 2,820 BrS cases and 10,001 controls revealed 21 genetic signals across 12 locations, suggesting a strong genetic component to the disorder.
  • Key findings highlight the importance of transcription regulation in BrS development and introduce microtubule-related mechanisms that affect the expression of a key cardiac protein, shedding light on the disorder's genetic and molecular basis.
View Article and Find Full Text PDF
Article Synopsis
  • Heart failure is when the heart can't pump blood well, often caused by heart diseases or problems with the heart muscle, called cardiomyopathies.
  • The Maastricht Cardiomyopathy registry aims to help doctors diagnose and treat these heart problems better and earlier.
  • They are collecting a lot of patient information over 15 years to find patterns and improve treatment, and other medical centers can easily join the research too.
View Article and Find Full Text PDF

Aims: Global longitudinal strain (GLS) has become an alternative to left ventricular ejection fraction (LVEF) to determine systolic function of the heart. The absence of cut-off values is one of the limitations preventing full clinical implementation. The aim of this study is to determine a cut-off value of GLS for an increased risk of adverse events in individuals with a normal LVEF.

View Article and Find Full Text PDF

Purpose: Accurate interpretation of variants detected in dilated cardiomyopathy (DCM) is crucial for patient care but has proven challenging. We applied a set of proposed refined American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria for DCM, reclassified all detected variants in robust genes, and associated these results to patients' phenotype.

Methods: The study included 902 DCM probands from the Maastricht Cardiomyopathy Registry who underwent genetic testing.

View Article and Find Full Text PDF