A5018231465- Genetic Syndromes and Imprinting
- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Neurogenetic and Muscular Disorders Research
- Epigenetics and DNA Methylation
- Hereditary Neurological Disorders
- RNA modifications and cancer
- Neurological diseases and metabolism
- Congenital Anomalies and Fetal Surgery
- Genomics and Rare Diseases
- Genetic Neurodegenerative Diseases
- Chromosomal and Genetic Variations
- Genetics and Neurodevelopmental Disorders
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Botulinum Toxin and Related Neurological Disorders
- Renal and related cancers
- Genetic Associations and Epidemiology
- Protein Tyrosine Phosphatases
- Obsessive-Compulsive Spectrum Disorders
- RNA regulation and disease
- Kruppel-like factors research
- Peripheral Neuropathies and Disorders
RWTH Aachen University
2013-2025
Universitätsklinikum Aachen
2006-2025
Polish Academy of Sciences
2020
Ludwig-Maximilians-Universität München
2020
Dr. John T. Macdonald Foundation
2020
Mossakowski Medical Research Institute, Polish Academy of Sciences
2020
University Hospital Ulm
2015
University Medical Center Freiburg
2015
University of Lübeck
2015
University of Tübingen
1998-2002
Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. Since motor neuron injury usually not reversible, early diagnosis and treatment are essential to prevent major disability. Our objective was assess impact of genetic newborn screening for SMA on outcome. We provided clinical data from 43 patients, identified via polymerase chain reaction SMN1 gene dried blood spots between January 2018 2020 Germany. Follow-up included neurophysiological examinations...
Homozygous deletions/mutations of the SMN1 gene cause infantile spinal muscular atrophy (SMA). The presence at least one SMN2 copy is required for normal embryogenesis. Lack SMN protein results in degeneration motor neurons, while extraneuronal manifestations have been regarded as a chance association with SMA. We report on heart defects subgroup congenital SMA type I patients.Data were recruited from 65 unselected patients whose diagnosis had confirmed genetically within first 6 months age....
We present clinical features and genetic results of 1206 index patients 124 affected relatives who were referred for testing Charcot-Marie-Tooth (CMT) neuropathy at the laboratory in Aachen between 2001 2012. Genetic detection rates 56% demyelinating CMT (71% autosomal dominant (AD) CMT1/CMTX), 17% axonal (24% AD CMT2/CMTX). Three defects (PMP22 duplication/deletion, GJB1/Cx32 or MPZ/P0 mutation) responsible 89.3% whom a diagnosis was achieved, diagnostic yield three main (GJB1/Cx32, MFN2,...
Molecular genetic testing for the 11p15-associated imprinting disorders Silver–Russell and Beckwith–Wiedemann syndrome (SRS, BWS) is challenging because of molecular heterogeneity complexity affected imprinted regions. With growing knowledge on basis these demand testing, it turned out that there an urgent need a standardized diagnostic reporting strategy. Based results from first external pilot quality assessment schemes organized by European Quality Network (EMQN) in 2014 context with...
Although the value of newborn screening (NBS) for early detection and treatment opportunity in SMA patients is generally accepted, there still an ongoing discussion about best strategy children with 4 more copies SMN2 gene. This gene known to be most important but not only disease modifier. In our SMA-NBS pilot project Germany comprising 278,970 infants screened between January 2018 November 2019 were 38 positive cases a homozygous SMN1 deletion. 40% them had or copies. The incidence...
Small fiber neuropathy (SFN) is increasingly suspected in patients with pain of uncertain origin, and making the diagnosis remains a challenge lacking diagnostic gold standard.In this case-control study, we prospectively recruited 86 medical history clinical phenotype suggestive SFN. Patients underwent neurological examination, quantitative sensory testing (QST), distal proximal skin punch biopsy, were tested for pain-associated gene loci. Fifty-five these additionally pain-related evoked...
We reviewed the natural history and assessed SMN2 copy number of 66 patients with infantile spinal muscular atrophy (SMA) type I born between 2000 2005 in Germany whose diagnosis was confirmed by a homozygous SMN1 deletion first 6 months life. After excluding who had received valproic acid, median/mean age at disease endpoint 6.1/7.3 (range 0.0–34.0). Four (6.1%) one severe SMA ‘0’ joint contractures respiratory distress from birth. Median/mean onset (months) 57 (86.3%) two copies 1.2/1.3,...
Early treatment after genetic newborn screening (NBS) for SMA significantly improves outcomes in infantile SMA. However, there is no consensus the community about early initiation patients with four copies of SMN2.Approach to a responsible strategy SMN2 detected screening.Inclusion criteria were history diagnosed by NBS, age > 12 months at last examination, and diagnosis confirmatory diagnosis.21 identified German projects over three-year period. In three them, copy number had be corrected...
Congenital insensitivity to pain (CIP) and hereditary sensory autonomic neuropathies (HSAN) are clinically genetically heterogeneous disorders exclusively or predominantly affecting the neurons. Due rarity of diseases findings based mainly on single case reports small series, knowledge about these is limited. Here, we describe molecular workup a large international cohort CIP/HSAN patients including from normally under-represented countries. We identify 80 previously unreported pathogenic...
Now that targeted therapies for spinal muscular atrophy are available, attempts being made worldwide to include screening in general newborn screening. In Germany, after pilot projects from 2018-2021, it was included the October 2021. To ensure a smooth transition, criteria follow-up were developed together with key stakeholders. At beginning of transition nationwide screening, false positive findings reported 3 patients. After optimization method laboratories concerned, all have been...
To test the hypothesis that monogenic neuropathies such as Charcot-Marie-Tooth disease (CMT) contribute to frequent but often unexplained in elderly, we performed genetic analysis of 230 patients with axonal and onset ≥35 years.We recruited patients, collected clinical data, conducted whole-exome sequencing (WES; n = 126) MME single-gene (n 104). We further queried WES repositories for variants measured blood levels MME-encoded protein neprilysin.In cohort, overall detection rate assumed...
Abstract Aims MICU1 encodes the gatekeeper of mitochondrial Ca 2+ uniporter, and biallelic loss‐of‐function mutations cause a complex, neuromuscular disorder in children. Although role protein is well understood, precise molecular pathophysiology leading to this neuropaediatric phenotype has not been fully elucidated. Here we aimed obtain novel insights into pathophysiology. Methods Molecular genetic studies along with proteomic profiling, electron‐, light‐ Coherent anti‐Stokes Raman...
Silver–Russell syndrome (SRS) describes a malformation with severe intrauterine and postnatal growth retardation. Currently, two major (epi)mutations have been described: while approximately 10% of patients carry maternal uniparental disomy chromosome 7 (UPD7), 35–60% show hypomethylation at the H19 differentially methylated regions (DMRs) in 11p15. Until recently, Southern‐blot based test was routinely used to identify epimutation carriers. Nevertheless, this time consuming hampered by huge...
Small supernumerary marker chromosomes (SMC) are a heterogeneous group of with an estimated frequency approximately 0.14–0.72 per 1000 newborns and higher frequencies in particular populations such as the mentally retarded or infertile males. With about 50%, derivatives chromosome 15 represent most common SMC. Here we present results detailed analysis 32 SMC(15) carriers who were ascertained pre‐ post‐natal routine cytogenetic diagnostics. euchromatic content led to mental psychomotor...
Silver–Russell syndrome ( SRS ) is a growth retardation characterized by intrauterine and postnatal retardation, relative macrocephaly protruding forehead, body asymmetry feeding difficulties. Nearly 50% of cases show hypomethylation in 11p15.5, 10% maternal uniparental disomy chromosome 7 present. A significant number patients with features also exhibit chromosomal aberrations. We analyzed 43 individuals referred for genetic testing molecular karyotyping. Pathogenic variants could be...
Heterozygous BICD2 gene mutations cause a form of autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED).We analyzed the in selected group 25 index patients neurogenic muscle atrophy.We identified 2 new missense mutations, c.2515G>A, p.Gly839Arg, family inheritance, and c.2202G>T, p.Lys734Asn, as de novo mutation an isolated patient similar phenotype. The had congenital foot contractures, legs, slowly progressive weakness shoulder girdle. There was no apparent...
Altered autophagy accompanied by abnormal autophagic (rimmed) vacuoles detectable light and electron microscopy is a common denominator of many familial sporadic non-inflammatory muscle diseases. Even in the era next generation sequencing (NGS), late-onset vacuolar myopathies remain diagnostic challenge. We identified 32 adult myopathy patients from 30 unrelated families, studied their clinical, histopathological ultrastructural characteristics performed genetic testing index relatives using...