8 results on '"Peter Huppke"'
Search Results
2. From ventriculomegaly to severe muscular atrophy: Expansion of the clinical spectrum related to mutations in AIFM1
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Peter Huppke, Lars Klinge, Matthias Kettwig, Franz A. Zimmermann, Saskia Biskup, Jutta Gärtner, Wolfgang Sperl, Johannes A. Mayr, and Max Schubach
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Adult ,Male ,Mitochondrial Diseases ,AIFM1 ,Ataxia ,Adolescent ,Mutation, Missense ,Biology ,Bioinformatics ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,Muscular Diseases ,medicine ,Humans ,Missense mutation ,Child ,Myopathy ,Molecular Biology ,Exome ,030304 developmental biology ,Family Health ,Genetics ,0303 health sciences ,Muscle biopsy ,medicine.diagnostic_test ,Genetic Diseases, Inborn ,Infant, Newborn ,Apoptosis Inducing Factor ,Infant ,Neurodegenerative Diseases ,Cell Biology ,medicine.disease ,3. Good health ,Child, Preschool ,Molecular Medicine ,Mutant Proteins ,medicine.symptom ,030217 neurology & neurosurgery ,Ventriculomegaly - Abstract
The apoptosis-inducing factor (AIF) functions as a FAD-dependent NADH oxidase in mitochondria. Upon apoptotic stimulation it is released from mitochondria and migrates to the nucleus where it induces chromatin condensation and DNA fragmentation. So far mutations in AIFM1, a X-chromosomal gene coding for AIF, have been described in three families with 11 affected males. We report here on a further patient thereby expanding the clinical and mutation spectrum. In addition, we review the known phenotypes related to AIFM1 mutations. The clinical course in the male patient described here was characterized by phases with rapid deterioration and long phases without obvious progression of disease. At age 2.5 years he developed hearing loss and severe ataxia and at age 10 years muscle wasting, swallowing difficulties, respiratory insufficiency and external opthamoplegia. By next generation sequencing of whole exome we identified a hemizygous missense mutation in the AIFM1 gene, c.727G>T (p.Val243Leu) affecting a highly conserved residue in the FAD-binding domain. Summarizing what is known today, mutations in AIFM1 are associated with a progressive disorder with myopathy, ataxia and neuropathy. Severity varies greatly even within one family with onset of symptoms between birth and adolescence. 3 of 12 patients died before age 5 years while others were still able to walk during young adulthood. Less frequent symptoms were hearing loss, seizures and psychomotor regression. Results from clinical chemistry, brain imaging and muscle biopsy were unspecific and inconsistent.
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- 2015
3. Pregnancy and Infant Outcomes with Interferon Beta: Data from the European Interferon Beta Pregnancy Registry and Population Based Registries in Finland and Sweden
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Yvonne Geissbuehler, J. Klinger, Kjell-Morten Myhr, Asher Ornoy, Scott Montgomery, A. Adamo, Sarah Burkill, Pasi K. Korhonen, Meritxell Sabidó, Peter Huppke, Kerstin Hellwig, and Catrinel Popescu
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Pregnancy registry ,medicine.medical_specialty ,Pregnancy ,Interferon beta ,business.industry ,Obstetrics ,Multiple sclerosis ,General Medicine ,Population based ,030204 cardiovascular system & hematology ,medicine.disease ,Infant outcomes ,03 medical and health sciences ,0302 clinical medicine ,Neurology ,030220 oncology & carcinogenesis ,Medicine ,Neurology (clinical) ,business - Published
- 2018
4. Treatment of epilepsy in Rett syndrome
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Georg M. Stettner, Peter Huppke, Knut Brockmann, Jutta Gärtner, and Karola Köhler
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Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Methyl-CpG-Binding Protein 2 ,Rett syndrome ,Disease-Free Survival ,MECP2 ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Female patient ,Rett Syndrome ,Humans ,Medicine ,Statistical analysis ,MECP2 gene ,Child ,Retrospective Studies ,030304 developmental biology ,0303 health sciences ,business.industry ,Retrospective cohort study ,General Medicine ,Carbamazepine ,Middle Aged ,medicine.disease ,3. Good health ,Treatment Outcome ,Child, Preschool ,Anesthesia ,Mutation ,Pediatrics, Perinatology and Child Health ,Anticonvulsants ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Introduction Epilepsy is very frequent in Rett syndrome (RTT) patients and often difficult to treat. Because most cases of RTT are caused by mutations in the MECP2 gene it is reasonable to assume that convulsions are based on common pathogenetic mechanisms and thus should have a similar response to antiepileptic drugs. Purpose: To find the optimal treatment for epilepsy in RTT. Methods We performed a retrospective study on 110 female patients with confirmed MECP2 mutations. Results The median age was 10 years, 58% had a history of epilepsy and 55% received antiepileptic drugs (AEDs). Only sulthiame, carbamazepine and valproate were administered in an adequate frequency to allow statistical analysis. The best anticonvulsive results were seen in the RTT group that was treated with carbamazepine. Sulthiame was slightly less effective while valproate was significantly less effective. The rate of side effects was equivalent in all groups. In conclusion, carbamazepine should be recommended as first choice AED in RTT. If carbamazepine is not effective or not well tolerated sulthiame ought to be taken as second choice AED.
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- 2007
5. Indication for genetic testing: A checklist for Rett syndrome
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Karola Köhler, Peter Huppke, F. Hanefeld, and Franco Laccone
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congenital, hereditary, and neonatal diseases and abnormalities ,Pediatrics ,medicine.medical_specialty ,Pathology ,Chromosomal Proteins, Non-Histone ,Methyl-CpG-Binding Protein 2 ,Rett syndrome ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,Rett Syndrome ,medicine ,Humans ,Genetic Testing ,Positive test ,Child ,030304 developmental biology ,Genetic testing ,0303 health sciences ,medicine.diagnostic_test ,Minimal risk ,business.industry ,Forme fruste ,medicine.disease ,Checklist ,Test (assessment) ,DNA-Binding Proteins ,Repressor Proteins ,El Niño ,Child, Preschool ,Mutation ,Pediatrics, Perinatology and Child Health ,Female ,business ,030217 neurology & neurosurgery - Abstract
Objective We reevaluated 49 girls with either Rett syndrome (RTT) or features of RTT who had negative test results for mutations in the MECP2 gene and compared them with 49 girls who had positive test results. The girls with MECP2-positive results included 2 girls with forme fruste and 2 with congenital RTT. Study design Based on the original diagnostic criteria for RTT, we developed a 10-item checklist with a score ranging from 0 to 12. Results If only girls with a score of 8 or more had been tested, 46% of the girls without mutations would have been excluded from testing without missing a single girl with MECP2-positive results. Conclusions This checklist provides a simple aid for deciding whether or not a genetic test for RTT should be performed with only a minimal risk of missing girls with MECP2-positive results. (J Pediatr 2003;142:332-5)
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- 2003
6. Mutations in SLC33A1 Cause a Lethal Autosomal-Recessive Disorder with Congenital Cataracts, Hearing Loss, and Low Serum Copper and Ceruloplasmin
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Cornelia Brendel, Peter Huppke, Reinhard Ullmann, Lisbeth Birk Møller, Merle Hillebrand, Gudrun Nürnberg, Peter Nürnberg, Stephen G. Kaler, Orly Elpeleg, Peter Freisinger, Iris Marquardt, Callum Wilson, Shzeena Dad, Vera M. Kalscheuer, John Christodoulou, Georg Christoph Korenke, Jutta Gärtner, Gaele Pitelet, Ursula Gruber-Sedlmayr, and Stefan A. Haas
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Male ,medicine.medical_specialty ,Molecular Sequence Data ,Biology ,medicine.disease_cause ,Compound heterozygosity ,Severity of Illness Index ,Article ,Cataract ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cerebellum ,medicine ,Genetics ,Humans ,Genetics(clinical) ,Aceruloplasminemia ,Child ,Hearing Loss ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,Mutation ,Base Sequence ,030305 genetics & heredity ,Ceruloplasmin ,Chromosome Mapping ,Infant ,Membrane Transport Proteins ,Hep G2 Cells ,Disease gene identification ,medicine.disease ,3. Good health ,Endocrinology ,Child, Preschool ,Immunology ,Congenital cataracts ,biology.protein ,Menkes disease ,Female ,Chromosomes, Human, Pair 3 ,Erratum ,Copper deficiency ,030217 neurology & neurosurgery ,Copper - Abstract
Low copper and ceruloplasmin in serum are the diagnostic hallmarks for Menkes disease, Wilson disease, and aceruloplasminemia. We report on five patients from four unrelated families with these biochemical findings who presented with a lethal autosomal-recessive syndrome of congenital cataracts, hearing loss, and severe developmental delay. Cerebral MRI showed pronounced cerebellar hypoplasia and hypomyelination. Homozygosity mapping was performed and displayed a region of commonality among three families at chromosome 3q25. Deep sequencing and conventional sequencing disclosed homozygous or compound heterozygous mutations for all affected subjects in SLC33A1 encoding a highly conserved acetylCoA transporter (AT-1) required for acetylation of multiple gangliosides and glycoproteins. The mutations were found to cause reduced or absent AT-1 expression and abnormal intracellular localization of the protein. We also showed that AT-1 knockdown in HepG2 cells leads to reduced ceruloplasmin secretion, indicating that the low copper in serum is due to reduced ceruloplasmin levels and is not a sign of copper deficiency. The severity of the phenotype implies an essential role of AT-1 in proper posttranslational modification of numerous proteins, without which normal lens and brain development is interrupted. Furthermore, AT-1 defects are a new and important differential diagnosis in patients with low copper and ceruloplasmin in serum.
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- 2012
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7. Failure of pallidal deep brain stimulation in a case of rapid-onset dystonia parkinsonism (DYT12)
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Peter Huppke, Andreas Horn, S. Ebner, G.-H. Schneider, Christof Brücke, Andrea A. Kühn, J. Gärtner, and Andreas Kupsch
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Deep brain stimulation ,Neurology ,business.industry ,medicine.medical_treatment ,Rapid-Onset Dystonia Parkinsonism ,Medicine ,Neurology (clinical) ,business ,Neuroscience - Published
- 2013
8. Novel mechanisms of glucocorticoids in the treatment of multiple sclerosis
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Fred Lühder, Henrike J. Fischer, Mikael Simons, Nils Schweingruber, Holger M. Reichardt, and Peter Huppke
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0303 health sciences ,Chemistry ,T cell ,Immunology ,T-cell receptor ,Wild type ,Stimulation ,medicine.disease_cause ,Autoimmunity ,law.invention ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,Neurology ,Antigen ,law ,medicine ,Immunology and Allergy ,Suppressor ,Neurology (clinical) ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
wildtype peptide SIINFEKL or its altered peptide ligand variants (APLs) exhibiting decreased affinities (SIINFEKL N SIYNFEKL N SIIQFEKL N SIIVFEKL). As read out, we assessed TF-mediated changes of the proliferative T cell response as well as T effector functions. Using the setup described above we could demonstrate that the extent of TFmediated suppression of T cell proliferation correlated with the affinity of the stimulatory antigen, i.e. TF exerted strong suppressive effects upon high-affinity TCR stimulation but only modest suppressive effects upon low-affinity TCR stimulation. Importantly, under these conditions, the proliferative response to different antigen affinities per se in the absence of TFwas comparable.Moreover, TF-mediated suppressionwas more pronounced employing higher antigen concentrations. Our results provide for the first time experimental evidence of affinity-dependent effects of a drug employed for control of T cell mediated autoimmunity. Hence,we propose that TF is not a global immune suppressor but rather acts as a selective immune-modulator, which preferentially interferes with the expansion of high affinity T cell clones while in parallel permitting low-affinity-triggered T cell responses. This is the first description of a novel sophisticated mechanism of selective immunemodulation depending on the quality of T cell activation.
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- 2014
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