A5029709992- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Genetic Neurodegenerative Diseases
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- Prenatal Screening and Diagnostics
- Ion channel regulation and function
- Platelet Disorders and Treatments
- Cardiac electrophysiology and arrhythmias
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Neurogenetic and Muscular Disorders Research
- Birth, Development, and Health
- Congenital heart defects research
- Hereditary Neurological Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Adipose Tissue and Metabolism
- DNA Repair Mechanisms
- Fungal and yeast genetics research
- Pain Mechanisms and Treatments
Maastricht University
2015-2024
Maastricht University Medical Centre
2014-2024
University Medical Center
2016-2023
Florence (Netherlands)
2023
Institut thématique Génétique, génomique et bioinformatique
2022
Children's Memorial Health Institute
2019
Medical University of Warsaw
2019
Cardiovascular Institute Hospital
2010
Radboud University Nijmegen
1988-1999
University of Kansas Medical Center
1995
Abstract. Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in COL4A5 gene are responsible for more common X-linked dominant form disease. Considerable allelic heterogeneity has been observed. A “European Community Syndrome Concerted Action” established to delineate accurately AS phenotype and determine genotype-phenotype correlations large number...
ABSTRACT. Alport syndrome (AS) is a type IV collagen hereditary disease characterized by progressive hematuric nephritis, hearing loss, and ocular changes. Mutations in the COL4A5 gene are responsible for more common X-linked dominant form of much less severe girls women. A “European Community Syndrome Concerted Action” (ECASCA) group was established to delineate phenotype each gender determine genotype-phenotype correlations large number families. Data concerning 329 families, 250 them with...
The gene encoding α6(IV) collagen, COL4A6 , was identified on the human X chromosome in a head-to-head arrangement and within 452 base pairs of α5(IV) collagen gene, COL4A5 . In earlier studies, intragenic deletions were detected subset patients with Alport syndrome (AS), hereditary defect basement membranes. some families, AS cosegregates diffuse leiomyomatosis (DL), benign smooth muscle tumor diathesis. Here it is shown that AS-DL harbor disrupt both Thus, type IV may regulate...
A group of 22 unrelated patients with sporadic or non-X-linked Alport syndrome were screened for mutations in the non-collagenous domain type IV collagen alpha 3 (COL4A3) chain gene. The five 3'-exons this gene, located on chromosome 2qter, tested by single strand conformation polymorphism analysis and direct sequencing. One patient was heterozygous another homozygous (Mochizuki et al., Nature Genetics, press) a deletion nucleotides. third appeared to be compound heterozygote two different...
Background: The μ ‐opioid receptor gene ( OPRM1 ) codes for the receptor, which binds β ‐endorphin. A118G polymorphism in this affects ‐endorphin binding such that Asp40 variant (G allele) 3 times more tightly than common Asn40 (A allele). This study investigated influence of on cue reactivity after exposure to an alcoholic beverage male heavy drinkers. Methods: Participants were either homozygous A allele n =84) or carrying at least 1 copy G =24). All participants took part a cue‐reactivity...
Mutations in the receptor expression enhancing protein 1 (REEP1) have recently been reported to cause autosomal dominant hereditary spastic paraplegia (HSP) type SPG31. In a large collaborative effort, we screened sample of 535 unrelated HSP patients for REEP1 mutations and copy number variations. We identified 13 novel 2 known 16 familial sporadic by direct sequencing analysis. Twelve out were small insertions, deletions or splice site mutations. These changes would result shifts...
Mesenchymal stromal cells (MSCs) are multipotent stem with immunosuppressive and trophic support functions. While MSCs from different sources frequently display a similar appearance in culture, they often show differences their surface marker gene expression profiles. Although bone marrow is considered the "gold standard" tissue to isolate classical (BM-MSC), MSC-like currently also derived more easily accessible extra-embryonic tissues such as umbilical cord. In this study, we defined best...
Mitochondrial disorders, characterized by clinical symptoms and/or OXPHOS deficiencies, are caused pathogenic variants in mitochondrial genes. However, some of these genes can lead to manifestations which overlap with other neuromuscular diseases, be non-mitochondrial as well. found the DNA (mtDNA) or any 1,500 nuclear a function. We have performed two-step next-generation sequencing approach cohort 117 patients, mostly children, whom disease-cause could likely possibly explain phenotype. A...
Mitochondrial complex I deficiency is the most common oxidative phosphorylation defect. Mutations have been detected in mitochondrial and nuclear genes, but genetics of many patients remain unresolved new genes are probably involved. In a consanguineous family, presented easy fatigability, exercise intolerance lactic acidosis blood from early childhood. muscle, subsarcolemmal proliferation severe were observed. Exercise activity was improved by supplement riboflavin at high dosage....
Conflicting data exist on mitochondrial function and physical activity in type 2 diabetes mellitus (T2DM) development.The aim was to assess at different stages during T2DM development combination with exercise longstanding patients.We performed cross-sectional analysis of skeletal muscle from 12 prediabetic 11 male subjects controls matched by age body mass index.One-year intrasubject controlled supervised training intervention done patients.Extensive ex vivo analyses quality, quantity, were...
Leigh syndrome is an early onset, often fatal progressive neurodegenerative disorder caused by mutations in the mitochondrial or nuclear DNA. Until now, more than 35 genes have been reported to cause syndrome, indicating extreme genetic heterogeneity for this disorder, but still only explaining part of cases. The possibility whole exome sequencing enables not mutation detection known candidate genes, also identification new associated with small families and isolated Exome was combined...
<h3>Background</h3> Mitochondrial or oxidative phosphorylation diseases are relatively frequent, multisystem disorders; in about 15% of cases they caused by maternally inherited mitochondrial DNA (mtDNA) mutations. Because the possible severity phenotype, lack effective treatment, and high recurrence risk for offspring carrier females, couples wish to prevent transmission these mtDNA disorders their offspring. Prenatal diagnosis is problematic several reasons, concern often poor correlation...
Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported individuals presenting with lactic acidosis and cardiomyopathy. We describe genetic, clinical biochemical findings a cohort 70 patients, whom 29 previously unpublished. found 34 known 18 unreported ACAD9. No patients harbored loss function mutations, indicating that this combination unlikely to...
Severe, disease-causing germline mitochondrial (mt)DNA mutations are maternally inherited or arise de novo. Strategies to prevent transmission generally available, but depend on recurrence risks, ranging from high/unpredictable for many familial mtDNA point very low sporadic, large-scale single deletions. Comprehensive data lacking novo mutations, often leading misconceptions and incorrect counselling regarding risk reproductive options. We aim study the relevance of apparently...
With a combined carrier frequency of 1:200, heteroplasmic mitochondrial DNA (mtDNA) mutations cause human disease in ∼1:5000 the population. Rapid shifts level heteroplasmy seen within single generation contribute to wide range severity clinical phenotypes families transmitting mtDNA disease, consistent with genetic bottleneck during transmission. Although preliminary evidence from pedigrees points towards random drift process underlying shifting heteroplasmy, some reports describe...