Research Topics
Genomes and Genes | Brunhilde WirthSummaryAffiliation: University of Bonn Country: Germany Publications
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Detail Information
Publications
Different entities of proximal spinal muscular atrophy within one familyB Wirth
Institute of Human Genetics, Bonn, Germany
Hum Genet 100:676-80. 1997....
De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counselingB Wirth
Institute of Human Genetics, Bonn, Germany
Am J Hum Genet 61:1102-11. 1997..These findings have important implications for genetic counseling and prenatal diagnosis in that they emphasize the relevance of indirect genotype analysis in combination with direct SMN-gene deletion testing in SMA families...- Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counselingB Wirth
Institute of Human Genetics, Wilhelmstrasse 31, D 53111 Bonn, Germany
Am J Hum Genet 64:1340-56. 1999..We determined the validity of the test, and we discuss its practical implications and limitations... - An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA)B Wirth
Institute of Human Genetics, Bonn, Germany
Hum Mutat 15:228-37. 2000..The number of SMN2 copies modulates the SMA phenotype. Nevertheless, it should not be used for prediction of severity of the SMA... - Spinal muscular atrophy: state-of-the-art and therapeutic perspectivesBrunhilde Wirth
Institute of Human Genetics, University of Bonn, Germany
Amyotroph Lateral Scler Other Motor Neuron Disord 3:87-95. 2002..Since each SMA patient carries at least one SMN2 copy, reconstitution of full-length SMN2 protein is an exciting strategy for somatic gene therapy in SMA patients... 
SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophyMarkus Riessland
Institute of Human Genetics, University of Cologne, Cologne, Germany
Hum Mol Genet 19:1492-506. 2010..SMN RNA and protein levels were significantly elevated in various tissues including spinal cord and muscle. Hence, SAHA, which lessens the progression of SMA, might be suitable for SMA therapy...- In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophyEric Hahnen
Institute of Human Genetics, Institute of Genetics and Center for Molecular Medicine Cologne CMMC, University of Cologne, Cologne, Germany
J Neurochem 98:193-202. 2006..Because SAHA crosses the blood-brain barrier, oral administration may allow deceleration of progressive alpha-motoneurone degeneration by epigenetic SMN2 gene activation... - Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibitionJan Hauke
Institute of Human Genetics, University ofCologne, Cologne, Germany
Hum Mol Genet 18:304-17. 2009..These findings indicate that DNA methylation is functionally important regarding SMA disease progression and pharmacological SMN2 gene activation which might have implications for future SMA therapy regimens... - Nonsense-mediated messenger RNA decay of survival motor neuron 1 causes spinal muscular atrophyLars Brichta
Institute of Human Genetics, and Center for Molecular Medicine Cologne, University of Cologne, Kerpener Str 34, 50931, Cologne, Germany
Hum Genet 123:141-53. 2008..This study provides first evidence that NMD of SMN1 transcripts is responsible for the molecular basis of disease in a subset of SMA patients... - LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproateLutz Garbes
Institute of Human Genetics, University of Cologne, Cologne, Germany
Hum Mol Genet 18:3645-58. 2009..Hence, LBH589, which is active already at nanomolar doses, is a highly promising candidate for SMA therapy... - Deficiency of the splicing factor Sfrs10 results in early embryonic lethality in mice and has no impact on full-length SMN/Smn splicingYlva Mende
Institute of Human Genetics, Center for Molecular Medicine Cologne, University of Cologne, Cologne 50931, Germany
Hum Mol Genet 19:2154-67. 2010..Surprisingly, deletion of Sfrs10 by recombinant Cre showed no impact on SMN2 splicing but increased SMN levels. Our findings highlight the complexity by which alternatively spliced exons are regulated in vivo... - Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-beta1Claudia Helmken
Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, 53111 Bonn, Germany
Hum Genet 114:11-21. 2003..Further insights into the molecular pathway and the identification of SMA modifying gene(s) may help to find additional targets for a therapy approach... - Spinal muscular atrophy and therapeutic prospectsBrunhilde Wirth
Institute of Human Genetics, Institute of Genetics, and Center for Molecular Medicine Cologne, University of Cologne, Kerpener Str. 34, 50931 Cologne, Germany
Prog Mol Subcell Biol 44:109-32. 2006..However, phase III double-blind placebo controlled clinical trials have to finally prove the efficacy of these drugs... - The benzamide M344, a novel histone deacetylase inhibitor, significantly increases SMN2 RNA/protein levels in spinal muscular atrophy cellsMarkus Riessland
Institute of Human Genetics, Institute of Genetics, and Center for Molecular Medicine Cologne, University of Cologne, Kerpener Str. 34, 50931 Cologne, Germany
Hum Genet 120:101-10. 2006..In conclusion, M344 can be considered as highly potent HDAC inhibitor which is active at low doses and therefore represents a promising candidate for a causal therapy of SMA... - Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophyGabriela E Oprea
Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany
Science 320:524-7. 2008..Our study suggests that defects in axonogenesis are the major cause of SMA, thereby opening new therapeutic options for SMA and similar neuromuscular diseases... - Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophyMarkus Feldkötter
Institute of Human Genetics, University Clinic, Rheinische Friedrich Wilhelms University Bonn, Bonn, Germany
Am J Hum Genet 70:358-68. 2002..On the basis of SMN2 copy number, we calculated the posterior probability that a child with homozygous absence of SMN1 will develop type I, type II, or type III SMA... - Spinal muscular atrophy: from gene to therapyBrunhilde Wirth
Institute of Human Genetics, Institute of Genetics and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
Semin Pediatr Neurol 13:121-31. 2006..Recently, in vivo activation of the SMN gene was shown in VPA-treated SMA patients and carriers. Clinical trials are underway to investigate the effect of VPA and PBA on motor function in SMA patients... - hnRNP-G promotes exon 7 inclusion of survival motor neuron (SMN) via direct interaction with Htra2-beta1Yvonne Hofmann
Institute of Human Genetics, University of Bonn, Bonn, Germany
Hum Mol Genet 11:2037-49. 2002..Finally, we suggest a model of how the exon 7 mRNA processing is regulated by the splicing factors identified so far... - In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproateLars Brichta
Institute of Human Genetics, University of Cologne, Cologne, Germany
Ann Neurol 59:970-5. 2006..INTERPRETATION: We provide first proof of the in vivo activation of a causative gene by valproic acid in an inherited disease and discuss strategies of monitoring drug response in patients... - No evidence for DUP25 in patients with panic disorder using a quantitative real-time PCR approachJohannes Schumacher
Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, 53111 Bonn, Germany
Hum Genet 114:115-7. 2003..0). Thus, our study does not support the hypothesis of an involvement of DUP25 in panic disorder... - Histone deacetylase inhibitors: possible implications for neurodegenerative disordersEric Hahnen
Institute of Human Genetics, Institute of Genetics, University of Cologne, 50931 Cologne, Germany
Expert Opin Investig Drugs 17:169-84. 2008..Here, the authors summarize and discuss the findings on the emerging field of epigenetic therapy strategies in neurodegenerative disorders... - Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfectaJutta Becker
Institute of Human Genetics, University of Cologne, Cologne, Germany
Am J Hum Genet 88:362-71. 2011..PEDF is a multifunctional protein and one of the strongest inhibitors of angiogenesis currently known in humans. Our data provide genetic evidence for PEDF involvement in human bone homeostasis... - The zinc finger protein ZNF297B interacts with BDP1, a subunit of TFIIIBFrank Schoenen
Institute of Human Genetics, University of Cologne, D 50674 Cologne, Germany
Biol Chem 387:277-84. 2006..Immunofluorescence staining revealed a speckled pattern in the nuclei of HEK293 cells. Due to the essential role of BDP1 in Pol III transcription, we propose that ZNF297B may also regulate these transcriptional pathways... - Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2Matthew D Mailman
Department of Pathology, The Ohio State University, Columbus 43210, USA
Genet Med 4:20-6. 2002..A novel allele-specific intragenic mutation panel increases the sensitivity of SMN1 testing... - An approximately 140-kb deletion associated with feline spinal muscular atrophy implies an essential LIX1 function for motor neuron survivalJohn C Fyfe
Laboratory of Comparative Medical Genetics, Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48824, USA
Genome Res 16:1084-90. 2006..Nonetheless, a LIX1-associated etiology in feline SMA implicates a previously undetected mechanism of motor neuron maintenance and mandates consideration of LIX1 as a candidate gene in human SMA when SMN1 mutations are not found... - Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophySabine Rudnik-Schoneborn
Institute for Human Genetics, RWTH Aachen University, Pauwelsstr 30, 52074 Aachen, Germany
Neurogenetics 8:137-42. 2007..Particularly, if neurogenic atrophy is combined with a cardiac disease in a family, this should prompt LMNA mutation analysis... - X-linked infantile spinal muscular atrophy: clinical definition and molecular mappingDevin Dressman
Research Center for Genetic Medicine, Children s National Medical Center, Washington, DC, USA
Genet Med 9:52-60. 2007..3-q11.2. Here we report further clinical description of XL-SMA plus an additional seven unrelated (XL-SMA) families from North America and Europe that show linkage data consistent with the same region... - Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophySabine Rudnik-Schoneborn
Institute for Human Genetics, Aachen University, Aachen, Germany
Am J Med Genet A 117:10-7. 2003..The genetic basis of PCH-1 remains to be determined. The gene locus for infantile SMA on chromosome 5q could be excluded by linkage studies. Parental consanguinity and affected siblings make autosomal recessive inheritance most likely...