Najim Lahrouchi
A5066092517- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- Genetic Associations and Epidemiology
- Congenital heart defects research
- Cardiovascular Effects of Exercise
- Ion channel regulation and function
- Genomics and Rare Diseases
- Congenital Heart Disease Studies
- Cardiac pacing and defibrillation studies
- ECG Monitoring and Analysis
- Nutrition, Genetics, and Disease
- Cardiac Arrhythmias and Treatments
- Coronary Artery Anomalies
- Ocular Oncology and Treatments
- Genetic Mapping and Diversity in Plants and Animals
- RNA and protein synthesis mechanisms
- Retinal and Macular Surgery
- Hormonal Regulation and Hypertension
- Genetics and Neurodevelopmental Disorders
- Glaucoma and retinal disorders
- Viral Infections and Immunology Research
- Vascular Tumors and Angiosarcomas
- Connective tissue disorders research
- 14-3-3 protein interactions
- Head and Neck Surgical Oncology
Amsterdam Neuroscience
2019-2023
University of Amsterdam
2014-2022
Amsterdam University Medical Centers
2016-2022
Broad Institute
2018-2021
Massachusetts General Hospital
2019-2021
ERN GUARD-Heart
2019-2020
Harvard University
2019
Amsterdam UMC Location University of Amsterdam
2014-2018
Netherlands Heart Institute
2016
Fondazione Salvatore Maugeri
2015
Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular has a signature genetic theme. Hypertrophic are largely understood diseases sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing complex diverse architecture. To clarify this, systematic curation evidence to establish relationship with DCM was conducted.
Sudden arrhythmic death syndrome (SADS) describes a sudden with negative autopsy and toxicological analysis. Cardiac genetic disease is likely etiology.
Abstract Aims Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1–3) that encode identical calmodulin proteins. We established International Calmodulinopathy Registry (ICalmR) to understand natural history, clinical features, response therapy patients with a CALM-mediated syndrome. Methods results A dedicated Case Report File was created collect demographic, clinical, genetic...
Long QT syndrome (LQTS) is a rare genetic disorder and major preventable cause of sudden cardiac death in the young. A causal variant with large effect size identified up to 80% probands (genotype positive) cascade family screening shows incomplete penetrance variants. Furthermore, proportion cases meeting diagnostic criteria for LQTS remain genetically elusive despite testing established genes negative). These observations raise possibility that common variants small contribute clinical...
Abstract Aims Sodium-channel blockers (SCBs) are associated with arrhythmia, but variability of cardiac electrical response remains unexplained. We sought to identify predictors ajmaline-induced PR and QRS changes Type I Brugada syndrome (BrS) electrocardiogram (ECG). Methods results In 1368 patients that underwent ajmaline infusion for suspected BrS, we performed measurements 26 721 ECGs, dose–response mixed modelling genotyping. calculated polygenic risk scores (PRS) interval (PRSPR),...
Stringent variant interpretation guidelines can lead to high rates of variants uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada (BrS). Quantitative disease-specific customization American College Medical Genetics Genomics/Association Molecular Pathology (ACMG/AMP) address this false negative rate.We compared rare frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) 3335 BrS (SCN5A) cases the International LQTS/BrS Consortia...
Abstract The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration JT interval, respectively. abnormalities are associated with potentially fatal arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 121 independent loci for QT, QRS, respectively, including a male-specific X-chromosome locus. gene-based rare-variant methods, associations Mendelian disease...
Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports D-TGA patients with rare variants individual genes, majority cases remain genetically elusive. Familial recurrence patterns and observation that most sporadic suggest polygenic inheritance for disorder, yet this remains unexplored. Objective: We sought to study role common single nucleotide polymorphisms (SNPs)...
Abstract A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated homozygous frameshift mutations FAT1 . We show that Fat1 knockout mice zebrafish embryos for truncating fat1a exhibit completely penetrant coloboma, recapitulating most consistent developmental defect observed affected individuals....
The first human mutations in GATA6 were described a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores broad by presenting two de novo mutations, both exhibiting complex cardiac defects, pancreatic, other abnormalities. Furthermore, we provided detailed overview all published genetic variation in/near to date associated phenotypes (n = 78). We conclude that most common mutation structural pancreatic...
Congenital heart disease is the most common type of birth defect, accounting for one-third all congenital anomalies. Using whole-exome sequencing 2718 patients with and a search in GeneMatcher, we identified 30 from 21 unrelated families different ancestries biallelic phospholipase D1 (PLD1) variants who presented predominantly cardiac valve defects. We also associated recessive PLD1 isolated neonatal cardiomyopathy. Furthermore, established that p.I668F founder variant among Ashkenazi Jews...
Background: The cardiomyopathies are classically categorized as hypertrophic (HCM), dilated (DCM), and arrhythmogenic right ventricular (ARVC), each have a signature genetic theme. HCM ARVC largely understood diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning more than 10 gene ontologies been implicated in DCM, representing complex diverse architecture. To clarify this, systematic curation evidence to establish the relationship with DCM was...