Erik‐Jan Kamsteeg
A5087332579- Genetic Neurodegenerative Diseases
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Ion Transport and Channel Regulation
- Hereditary Neurological Disorders
- Cellular transport and secretion
- Neurogenetic and Muscular Disorders Research
- Metabolism and Genetic Disorders
- Neurological diseases and metabolism
- Genomic variations and chromosomal abnormalities
- Nuclear Structure and Function
- RNA modifications and cancer
- Glycogen Storage Diseases and Myoclonus
- Cardiovascular Effects of Exercise
- Diet and metabolism studies
- Cardiac electrophysiology and arrhythmias
- Electrolyte and hormonal disorders
- Muscle and Compartmental Disorders
- Genomics and Phylogenetic Studies
- Myasthenia Gravis and Thymoma
- Ubiquitin and proteasome pathways
Radboud University Nijmegen
2016-2025
Radboud University Medical Center
2016-2025
University Medical Center
2017-2024
Assistance Publique – Hôpitaux de Paris
2024
Institut Mondor de Recherche Biomédicale
2024
Biomedical Research Institute
2024
Université Paris-Est Créteil
2024
Inserm
2024
Rijnstate Hospital
2024
SPZ Frankfurt Mitte
2024
The advent of massive parallel sequencing is rapidly changing the strategies employed for genetic diagnosis and research rare diseases that involve a large number genes. So far it not clear whether these approaches perform significantly better than conventional single gene testing as requested by clinicians. current yield this traditional diagnostic approach depends on complex factors include gene-specific phenotype traits, relative frequency involvement specific To gauge impact paradigm...
Copy-number variation is a common source of genomic and an important genetic cause disease. Microarray-based analysis copy-number variants (CNVs) has become first-tier diagnostic test for patients with neurodevelopmental disorders, yield 10-20%. However, most other the role CNVs less clear studies are generally limited to study single-nucleotide (SNVs) small variants. With introduction exome genome sequencing, it now possible detect both SNVs using exome- or genome-wide approach single...
Mutations in the aquaporin-2 (AQP2) water channel gene cause autosomal recessive nephrogenic diabetes insipidus (NDI). Here we report first patient with an dominant form of NDI, which is caused by a G866A transition AQP2 one allele, resulting E258K substitution C-tail AQP2. To define molecular NDI this patient, AQP2-E258K was studied Xenopus oocytes. In contrast to wild-type AQP2, conferred small increase permeability, reduced expression at plasma membrane. Coexpression AQP2-E258K, but not...
To regulate mammalian water homeostasis, arginine-vasopressin (AVP) induces phosphorylation and thereby redistribution of renal aquaporin-2 (AQP2) channels from vesicles to the apical membrane. Vice versa, AVP (or forskolin) removal hormones activating PKC cause AQP2 internalization, but mechanism is unknown. Here, we show that a fraction modified with two three ubiquitin moieties in vitro vivo. Mutagenesis revealed ubiquitinated one K63-linked chain at K270 only. In Madin-Darby canine...
Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 with tyrosine reviewed the literature. Based presenting neurological features, can be divided two phenotypes: infantile onset, progressive,...
Myotonic dystrophy is an autosomal dominant, multisystem disorder that characterized by myotonic myopathy. The symptoms and severity of type l (DM1) ranges from severe congenital forms, which frequently result in death because respiratory deficiency, through to late-onset baldness cataract. In adult patients, cardiac conduction abnormalities may occur cause a shorter life span. subsequent generations, the DM1 present at earlier age have more course (anticipation). 2 (DM2), no anticipation...
Objective To identify novel causes of recessive ataxias, including spinocerebellar ataxia with saccadic intrusions, spastic and paraplegia. Methods In an international collaboration, we independently performed exome sequencing in 7 families and/or evaluate the role VPS13D mutations, evaluated a Drosophila knockout model investigated mitochondrial function patient‐derived fibroblast cultures. Results Exome identified compound heterozygous mutations on chromosome 1p36 all families. This...
Several known or putative glycosyltransferases are required for the synthesis of laminin-binding glycans on alpha-dystroglycan (αDG), including POMT1, POMT2, POMGnT1, LARGE, Fukutin, FKRP, ISPD and GTDC2. Mutations in these glycosyltransferase genes result defective αDG glycosylation reduced ligand binding by causing a clinically heterogeneous group congenital muscular dystrophies, commonly referred to as dystroglycanopathies. The most severe clinical form, Walker–Warburg syndrome (WWS), is...
Jeune asphyxiating thoracic dystrophy (JATD) is a rare, often lethal, recessively inherited chondrodysplasia characterised by shortened ribs and long bones, sometimes accompanied polydactyly, renal, liver retinal disease. Mutations in intraflagellar transport (IFT) genes cause JATD, including the IFT dynein-2 motor subunit gene DYNC2H1. Genetic heterogeneity large DYNC2H1 size have hindered JATD genetic diagnosis.To determine contribution to we screened 71 patients combining SNP mapping,...
Objective Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management this important emerging disorder. Methods Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans . We then undertook a detailed analysis the clinical, histopathological imaging features these patients. Results All had prenatal or early onset hypotonia contractures. None...
Background and purpose Although several recent studies have implicated RYR 1 mutations as a common cause of various myopathies the malignant hyperthermia susceptibility ( MHS ) trait, many these been limited to certain age groups, confined geographical regions or specific conditions. The aim present study was investigate full spectrum ‐related disorders throughout life use this knowledge increase vigilance concerning hyperthermia. Methods A retrospective cohort performed on clinical, genetic...
Spastic paraplegia type 7 is an autosomal recessive neurodegenerative disorder mainly characterized by progressive bilateral lower limb spasticity and referred to as a form of hereditary spastic paraplegia. Additional disease features may also be observed part more complex phenotype. Many different mutations have already been identified, but no genotype–phenotype correlations found so far. From total almost 800 patients for testing, we identified 60 with in the SPG7 gene. We 14 previously...
Cerebellar ataxia (CA) and hereditary spastic paraplegia (HSP) are two of the most prevalent motor disorders with extensive locus allelic heterogeneity. We implemented clinical exome sequencing, followed by filtering data for a ‘movement disorders’ gene panel, as generic test to increase variant detection in 76 patients these disorders. Segregation analysis or phenotypic re-evaluation was utilized substantiate findings. Disease-causing variants were identified 9 28 CA patients, 8 48 HSP...
Objectives The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number causative genes have not yet been recognized. We aimed to investigate this paucity diagnoses. Methods undertook weighted burden analysis whole‐exome sequencing (WES) data from 138 individuals unresolved generalized etiology, followed by additional case‐finding international databases, first for the gene implicated ( VPS16 ), and then other functionally...
Approximately two third of patients with a rare genetic disease remain undiagnosed after exome sequencing (ES). As part our post-test counseling procedures, without conclusive diagnosis are advised to recontact their referring clinician discuss new diagnostic opportunities in due time. We performed systematic study genetically 5 years initial negative ES report determine the efficiency diverse reanalysis strategies.We revisited cohort 150 pediatric neurology originally enrolled at Radboud...