Brunhilde Wirth

Summary

Affiliation: University of Bonn
Country: Germany

Publications

  1. ncbi Different entities of proximal spinal muscular atrophy within one family
    B Wirth
    Institute of Human Genetics, Bonn, Germany
    Hum Genet 100:676-80. 1997
  2. ncbi Spinal muscular atrophy: state-of-the-art and therapeutic perspectives
    Brunhilde Wirth
    Institute of Human Genetics, University of Bonn, Germany
    Amyotroph Lateral Scler Other Motor Neuron Disord 3:87-95. 2002
  3. ncbi 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
  4. pmc 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 counseling
    B Wirth
    Institute of Human Genetics, Wilhelmstrasse 31, D 53111 Bonn, Germany
    Am J Hum Genet 64:1340-56. 1999
  5. pmc De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling
    B Wirth
    Institute of Human Genetics, Bonn, Germany
    Am J Hum Genet 61:1102-11. 1997
  6. ncbi In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy
    Eric 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
  7. doi SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophy
    Markus Riessland
    Institute of Human Genetics, University of Cologne, Cologne, Germany
    Hum Mol Genet 19:1492-506. 2010
  8. doi Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality
    Bastian Ackermann
    Institute of Human Genetics, University of Cologne, Kerpener Strasse 34, Cologne, Germany
    Hum Mol Genet 22:1328-47. 2013
  9. pmc Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition
    Jan Hauke
    Institute of Human Genetics, University ofCologne, Cologne, Germany
    Hum Mol Genet 18:304-17. 2009
  10. doi Nonsense-mediated messenger RNA decay of survival motor neuron 1 causes spinal muscular atrophy
    Lars 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

Collaborators

Detail Information

Publications34

  1. ncbi Different entities of proximal spinal muscular atrophy within one family
    B Wirth
    Institute of Human Genetics, Bonn, Germany
    Hum Genet 100:676-80. 1997
    ....
  2. ncbi Spinal muscular atrophy: state-of-the-art and therapeutic perspectives
    Brunhilde 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...
  3. ncbi 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...
  4. pmc 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 counseling
    B 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...
  5. pmc De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling
    B 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...
  6. ncbi In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy
    Eric 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...
  7. doi SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophy
    Markus 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...
  8. doi Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality
    Bastian Ackermann
    Institute of Human Genetics, University of Cologne, Kerpener Strasse 34, Cologne, Germany
    Hum Mol Genet 22:1328-47. 2013
    ..Indeed, ubiquitous over-expression moderately improved survival and motor function in SMA mice. As PLS3 seems to act independently of Smn, PLS3 might be a potential therapeutic target not only in SMA but also in other MN diseases...
  9. pmc Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition
    Jan 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...
  10. doi Nonsense-mediated messenger RNA decay of survival motor neuron 1 causes spinal muscular atrophy
    Lars 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...
  11. doi 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 valproate
    Lutz 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...
  12. pmc Severe SMA mice show organ impairment that cannot be rescued by therapy with the HDACi JNJ-26481585
    Julia Schreml
    Institute of Human Genetics, University of Cologne, Cologne, Germany
    Eur J Hum Genet 21:643-52. 2013
    ..A better understanding of - primary or secondary - non-neuromuscular organ involvement in SMA patients may improve standard of care and may lead to reassessment of how to investigate SMA patients clinically...
  13. doi Deficiency of the splicing factor Sfrs10 results in early embryonic lethality in mice and has no impact on full-length SMN/Smn splicing
    Ylva 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...
  14. ncbi Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-beta1
    Claudia 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...
  15. ncbi Spinal muscular atrophy and therapeutic prospects
    Brunhilde 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...
  16. pmc 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 atrophy
    Markus 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...
  17. ncbi The benzamide M344, a novel histone deacetylase inhibitor, significantly increases SMN2 RNA/protein levels in spinal muscular atrophy cells
    Markus 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...
  18. doi Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy
    Gabriela 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...
  19. ncbi Spinal muscular atrophy: from gene to therapy
    Brunhilde 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...
  20. ncbi hnRNP-G promotes exon 7 inclusion of survival motor neuron (SMN) via direct interaction with Htra2-beta1
    Yvonne 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...
  21. ncbi In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate
    Lars Brichta
    Institute of Human Genetics, University of Cologne, Cologne, Germany
    Ann Neurol 59:970-5. 2006
    ..Spinal muscular atrophy results from loss of the survival motor neuron 1 (SMN1) gene and malfunction of the remaining SMN2. We investigated whether valproic acid can elevate human SMN expression in vivo...
  22. ncbi No evidence for DUP25 in patients with panic disorder using a quantitative real-time PCR approach
    Johannes 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...
  23. ncbi Histone acetylation as a potential therapeutic target in motor neuron degenerative diseases
    Lutz Garbes
    Institute of Human Genetics, University of Cologne, Germany
    Curr Pharm Des 19:5093-104. 2013
    ..This review will summarize the advances of HDACi in MNDs and will give a perspective where the road will lead us. ..
  24. doi How genetic modifiers influence the phenotype of spinal muscular atrophy and suggest future therapeutic approaches
    Brunhilde Wirth
    Institute of Human Genetics, Institute for Genetics, Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
    Curr Opin Genet Dev 23:330-8. 2013
    ..We will outline how this knowledge contributes to understanding of the regulatory networks and molecular pathology of SMA and how this knowledge will influence future approaches to therapies. ..
  25. doi VPA response in SMA is suppressed by the fatty acid translocase CD36
    Lutz Garbes
    Institute of Human Genetics, Institute of Genetics and Center for Molecular Medicine Cologne, Germany
    Hum Mol Genet 22:398-407. 2013
    ..Increased CD36 expression accounts for VPA non-responsiveness. These findings may be essential not only for SMA but also for other diseases such as epilepsy or migraine frequently treated with VPA...
  26. doi Histone deacetylase inhibitors: possible implications for neurodegenerative disorders
    Eric 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...
  27. pmc Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta
    Jutta 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...
  28. ncbi The zinc finger protein ZNF297B interacts with BDP1, a subunit of TFIIIB
    Frank 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...
  29. pmc Neuronal-specific deficiency of the splicing factor Tra2b causes apoptosis in neurogenic areas of the developing mouse brain
    Markus Storbeck
    Institute of Human Genetics, University of Cologne, Cologne, Germany Institute of Genetics, University of Cologne, Cologne, Germany Center for Molecular Medicine, University of Cologne, Cologne, Germany
    PLoS ONE 9:e89020. 2014
    ..Apoptotic events triggered via p21 might not be restricted to the developing brain but could possibly be generalized to the whole organism and explain early embryonic lethality in Tra2b-depleted mice. ..
  30. ncbi Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2
    Matthew 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...
  31. ncbi Mutations of the LMNA gene can mimic autosomal dominant proximal spinal muscular atrophy
    Sabine 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...
  32. pmc An approximately 140-kb deletion associated with feline spinal muscular atrophy implies an essential LIX1 function for motor neuron survival
    John 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...
  33. ncbi Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy
    Sabine 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...
  34. ncbi X-linked infantile spinal muscular atrophy: clinical definition and molecular mapping
    Devin 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...