Johan T den Dunnen

Summary

Affiliation: Leiden University Medical Center
Country: The Netherlands

Publications

  1. ncbi request reprint Nomenclature for the description of human sequence variations
    J T den Dunnen
    MGC Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Genet 109:121-4. 2001
  2. ncbi request reprint [From gene to disease; the dystrophin gene involved in Duchenne and Becker muscular dystrophy]
    J T den Dunnen
    Afd Humane Genetica, Leids Universitair Medisch Centrum, Wassenaarseweg 72, 2333 AL Leiden
    Ned Tijdschr Geneeskd 146:364-7. 2002
  3. doi request reprint Sharing data between LSDBs and central repositories
    Johan T den Dunnen
    Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands
    Hum Mutat 30:493-5. 2009
  4. pmc Developing a set of ancestry-sensitive DNA markers reflecting continental origins of humans
    Paula Kersbergen
    Department of Human Biological Traces R and D, Netherlands Forensic Institute, PO Box 24044, 2490 AA The Hague, The Netherlands
    BMC Genet 10:69. 2009
  5. pmc Detection of mutations in the dystrophin gene via automated DHPLC screening and direct sequencing
    R R Bennett
    Division of Genetics, Children s Hospital, Boston, Massachusetts, USA
    BMC Genet 2:17. 2001
  6. ncbi request reprint Diagnosis of genetic abnormalities in developmentally delayed patients: a new strategy combining MLPA and array-CGH
    Marjolein Kriek
    Center for Human and Clinical Genetics, Leiden University Medical Center, RC Leiden, The Netherlands
    Am J Med Genet A 143:610-4. 2007
  7. ncbi request reprint Generation and characterization of transgenic mice with the full-length human DMD gene
    Peter A C 't Hoen
    Center for Human and Clinical Genetics, Leiden University Medical Center, Postal Zone S4 P, PO Box 9600, 2300 RC Leiden, The Netherlands
    J Biol Chem 283:5899-907. 2008
  8. pmc Therapeutic exon skipping for dysferlinopathies?
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Hum Genet 18:889-94. 2010
  9. doi request reprint Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon
    Melvin M Evers
    Department of Human Genetics, Leiden University Medical Center, The Netherlands
    Neurobiol Dis 58:49-56. 2013
  10. ncbi request reprint Gene expression profiling highlights defective myogenesis in DMD patients and a possible role for bone morphogenetic protein 4
    Ellen Sterrenburg
    Center for Human and Clinical Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZA Leiden, The Netherlands
    Neurobiol Dis 23:228-36. 2006

Detail Information

Publications81

  1. ncbi request reprint Nomenclature for the description of human sequence variations
    J T den Dunnen
    MGC Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Genet 109:121-4. 2001
    ..This document lists the existing recommendations and summarizes suggestions for the description of additional, more complex changes. Another version of this paper has been published in Hum Mut 15:7-12, 2000...
  2. ncbi request reprint [From gene to disease; the dystrophin gene involved in Duchenne and Becker muscular dystrophy]
    J T den Dunnen
    Afd Humane Genetica, Leids Universitair Medisch Centrum, Wassenaarseweg 72, 2333 AL Leiden
    Ned Tijdschr Geneeskd 146:364-7. 2002
    ..Fifteen years after the discovery of the dystrophin gene, mutations can be detected in 95% of the patients, while the remaining 5% are still hiding within this very large gene...
  3. doi request reprint Sharing data between LSDBs and central repositories
    Johan T den Dunnen
    Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands
    Hum Mutat 30:493-5. 2009
    ..The document has been circulated in the HGVS/LSDB community and was discussed extensively. Here we summarize these discussions and present the concluded recommendations for LSDB data sharing with central repositories...
  4. pmc Developing a set of ancestry-sensitive DNA markers reflecting continental origins of humans
    Paula Kersbergen
    Department of Human Biological Traces R and D, Netherlands Forensic Institute, PO Box 24044, 2490 AA The Hague, The Netherlands
    BMC Genet 10:69. 2009
    ..The identification and use of Ancestry-Sensitive Markers (ASMs), i.e. genetic polymorphisms facilitating the genetic reconstruction of geographical origins of individuals, is far from straightforward...
  5. pmc Detection of mutations in the dystrophin gene via automated DHPLC screening and direct sequencing
    R R Bennett
    Division of Genetics, Children s Hospital, Boston, Massachusetts, USA
    BMC Genet 2:17. 2001
    ..The aim of this project was to develop an effective and convenient method of finding all, or most, mutations in the dystrophin gene with only a moderate increase in cost...
  6. ncbi request reprint Diagnosis of genetic abnormalities in developmentally delayed patients: a new strategy combining MLPA and array-CGH
    Marjolein Kriek
    Center for Human and Clinical Genetics, Leiden University Medical Center, RC Leiden, The Netherlands
    Am J Med Genet A 143:610-4. 2007
  7. ncbi request reprint Generation and characterization of transgenic mice with the full-length human DMD gene
    Peter A C 't Hoen
    Center for Human and Clinical Genetics, Leiden University Medical Center, Postal Zone S4 P, PO Box 9600, 2300 RC Leiden, The Netherlands
    J Biol Chem 283:5899-907. 2008
    ..In addition, the hDMD mouse can be used to study the influence of the genomic context on deletion and recombination frequencies, genome stability, and gene expression regulation...
  8. pmc Therapeutic exon skipping for dysferlinopathies?
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Hum Genet 18:889-94. 2010
    ..We also show that DYSF exon skipping seems to be as straightforward as DMD exon skipping, as AONs to induce efficient skipping of four DYSF exons were readily identified...
  9. doi request reprint Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon
    Melvin M Evers
    Department of Human Genetics, Leiden University Medical Center, The Netherlands
    Neurobiol Dis 58:49-56. 2013
    ..These results suggest that exon skipping may be a novel therapeutic approach to reduce polyglutamine-induced toxicity in spinocerebellar ataxia type 3. ..
  10. ncbi request reprint Gene expression profiling highlights defective myogenesis in DMD patients and a possible role for bone morphogenetic protein 4
    Ellen Sterrenburg
    Center for Human and Clinical Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZA Leiden, The Netherlands
    Neurobiol Dis 23:228-36. 2006
    ..These results support the hypothesis that inefficient muscle regeneration is caused by impaired myoblast differentiation and impaired maintenance of the myotubes...
  11. ncbi request reprint Gene expression profiling to monitor therapeutic and adverse effects of antisense therapies for Duchenne muscular dystrophy
    Peter A C 't Hoen
    Leiden University Medical Center, Center for Human and Clinical Genetics, Room S 04 003, Postbus 9600, 2300 RC Leiden, The Netherlands
    Pharmacogenomics 7:281-97. 2006
    ....
  12. pmc Deep sequencing-based expression analysis shows major advances in robustness, resolution and inter-lab portability over five microarray platforms
    Peter A C 't Hoen
    The Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Nucleic Acids Res 36:e141. 2008
    ..We conclude that deep sequencing provides a major advance in robustness, comparability and richness of expression profiling data and is expected to boost collaborative, comparative and integrative genomics studies...
  13. ncbi request reprint Exploring the frontiers of therapeutic exon skipping for Duchenne muscular dystrophy by double targeting within one or multiple exons
    Annemieke Aartsma-Rus
    DMD Genetic Therapy Group, Center for Human and Clinical Genetics, Leiden University Medical Center, RC Leiden, The Netherlands
    Mol Ther 14:401-7. 2006
    ..We aimed at inducing larger multiexon-skipping stretches, such as exons 17-51, exons 42-55, and exons 45-59. However, this appeared complicated and may be dependent on cotranscriptional splicing and the size of the flanking introns...
  14. ncbi request reprint Targeted exon skipping in transgenic hDMD mice: A model for direct preclinical screening of human-specific antisense oligonucleotides
    Mattie Bremmer-Bout
    Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
    Mol Ther 10:232-40. 2004
    ..These data highlight the high sequence specificity of this therapy and present the hDMD mouse as a unique model to optimize human-specific exon skipping in vivo...
  15. pmc Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Am J Hum Genet 74:83-92. 2004
    ..In fact, we here demonstrate its feasibility in myotubes from a patient with an exon 48-50 deletion. The application of multiexon skipping may provide a more uniform methodology for a larger group of patients with DMD...
  16. pmc Targeting several CAG expansion diseases by a single antisense oligonucleotide
    Melvin M Evers
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 6:e24308. 2011
    ....
  17. pmc Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophy
    Dwi U Kemaladewi
    Center for Human and Clinical Genetics, Leiden University Medical Center, Postzone S4 P, PO Box 9600, Leiden, 2300RC, The Netherlands
    BMC Med Genomics 4:36. 2011
    ..In this study, we aim to knockdown myostatin by means of exon skipping, a technique which has been successfully applied to reframe the genetic defect of dystrophin gene in DMD patients...
  18. ncbi request reprint Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients
    Gijs W E Santen
    Center for Human and Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
    Hum Mutat 34:1519-28. 2013
    ..Distal limbs anomalies are most marked in ARID1A patients and least in SMARCB1 patients. Numbers are small however, and larger series are needed to confirm this correlation. ..
  19. pmc Novel protein-protein interactions inferred from literature context
    Herman H H B M van Haagen
    Biosemantics Association, Department of Human Genetics, Leiden University Medical Center, Leiden, and Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands
    PLoS ONE 4:e7894. 2009
    ..Our framework can be used for prioritizing potential interaction partners, hitherto undiscovered, for follow-up studies and to aid the generation of accurate protein interaction maps...
  20. pmc Genome-wide assessment of differential roles for p300 and CBP in transcription regulation
    Yolande F M Ramos
    Department of Molecular Cell Biology, Leiden University Medical Center, Postzone S4 0P, PO Box 9600, 2300 RC Leiden, The Netherlands
    Nucleic Acids Res 38:5396-408. 2010
    ..Taken together, our findings further elucidate the distinct roles of coactivators p300 and CBP in transcriptional regulation...
  21. ncbi request reprint A complex rearrangement on chromosome 22 affecting both homologues; haplo-insufficiency of the Cat eye syndrome region may have no clinical relevance
    Marjolein Kriek
    Center for Human and Clinical Genetics, Leiden University Medical Center, Einthovenweg, 2300 RC, Leiden, The Netherlands
    Hum Genet 120:77-84. 2006
    ..This study highlights the value of using different genomic approaches to unravel chromosomal alterations in order to study their phenotypic impact...
  22. pmc Experiences with array-based sequence capture; toward clinical applications
    Rowida Almomani
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Hum Genet 19:50-5. 2011
    ..Future arrays should contain probes from both DNA strands, and to obtain a more even coverage, one could add fewer probes from densely and more probes from sparsely covered regions...
  23. doi request reprint Accurate quantification of dystrophin mRNA and exon skipping levels in duchenne muscular dystrophy
    Pietro Spitali
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Lab Invest 90:1396-402. 2010
    ..The use of the same technique allows comparison between different groups working on exon skipping in the mdx mouse model...
  24. pmc Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle
    Yanchao Huang
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mol Genet 17:1855-66. 2008
    ..Thus, our findings suggest interconnectivity between both diseases by revealing a novel physiological role for CAPN3 in regulating the dysferlin protein complex...
  25. ncbi request reprint Large-scale gene expression analysis of human skeletal myoblast differentiation
    Ellen Sterrenburg
    Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
    Neuromuscul Disord 14:507-18. 2004
    ..Further study of these genes can bring new insights into the process of muscle differentiation, and they are candidate genes for neuromuscular disorders with an as yet unidentified cause...
  26. pmc Gene expression variation between mouse inbred strains
    Rolf Turk
    Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, Nederland
    BMC Genomics 5:57. 2004
    ..In this study, we investigated the effect of genetic background on expression profiles. We analysed the transcriptome of mouse hindlimb muscle of five frequently used mouse inbred strains using spotted oligonucleotide microarrays...
  27. ncbi request reprint Exome sequencing identifies a branch point variant in Aarskog-Scott syndrome
    Emmelien Aten
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 34:430-4. 2013
    ..Our results show that besides digging deeper to reveal nonobvious variants, isolation and analysis of RNA provides a valuable but under-appreciated tool to resolve cases with unknown genetic defects...
  28. doi request reprint Fine-tiling array CGH to improve diagnostics for α- and β-thalassemia rearrangements
    Marion Phylipsen
    Hemoglobinopathies Laboratory, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 33:272-80. 2012
    ....
  29. pmc CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes
    Matthew S Hestand
    The Center for Human and Clinical Genetics, Leiden University Medical Center, Postzone S4 0P, PO Box 9600, 2300 RC Leiden, The Netherlands
    BMC Bioinformatics 9:495. 2008
    ..Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments...
  30. doi request reprint Deep sequencing to reveal new variants in pooled DNA samples
    Astrid A Out
    Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 30:1703-12. 2009
    ..We describe custom bioinformatics and statistics to optimize detection of rare variants and to estimate required sequencing depth. Our results provide directions for designing high-throughput analyses of candidate genes...
  31. ncbi request reprint Detecting copy number changes in genomic DNA: MAPH and MLPA
    Stefan J White
    Center for Human and Clinical Genetics, Leiden University Medical Center, 2333 AL Leiden, Nederland
    Methods Cell Biol 75:751-68. 2004
  32. ncbi request reprint Therapeutic antisense-induced exon skipping in cultured muscle cells from six different DMD patients
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
    Hum Mol Genet 12:907-14. 2003
    ..These results document important progress towards a clinically applicable, small-molecule based therapy...
  33. ncbi request reprint Local dystrophin restoration with antisense oligonucleotide PRO051
    Judith C van Deutekom
    Department of Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    N Engl J Med 357:2677-86. 2007
    ..We explored the safety, adverse-event profile, and local dystrophin-restoring effect of a single, intramuscular dose of an antisense oligonucleotide, PRO051, in patients with this disease...
  34. pmc Intensity-based analysis of two-colour microarrays enables efficient and flexible hybridization designs
    Peter A C 't Hoen
    Center for Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    Nucleic Acids Res 32:e41. 2004
    ....
  35. doi request reprint Rapid and cost effective detection of small mutations in the DMD gene by high resolution melting curve analysis
    Rowida Almomani
    Center for Human and Clinical Genetics, LUMC, Einthovenweg 20, Leiden, The Netherlands
    Neuromuscul Disord 19:383-90. 2009
    ..Our results provide validation of HR-MCA as a powerful and inexpensive pre-sequencing scanning method. This technology is now ready for routine diagnostic use on DMD/BMD patients and female carriers...
  36. ncbi request reprint Functional analysis of 114 exon-internal AONs for targeted DMD exon skipping: indication for steric hindrance of SR protein binding sites
    Annemieke Aartsma-Rus
    Leiden University Medical Center, Center for Human and Clinical Genetics, 2333 AL Leiden, The Netherlands
    Oligonucleotides 15:284-97. 2005
    ..Our results suggest that effective exon-internal AONs primarily act by blocking SR binding sites (which often correspond to open structures) and that ESEfinder may be used to refine AON design for DMD and other genes...
  37. doi request reprint Leiden Open Variation Database of the MUTYH gene
    Astrid A Out
    Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 31:1205-15. 2010
    ..This open-access repository allows all involved to quickly share all variants encountered and communicate potential consequences, which will be especially useful to classify variants of uncertain significance...
  38. doi request reprint MLPA and MAPH: sensitive detection of deletions and duplications
    Johan T den Dunnen
    Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Curr Protoc Hum Genet . 2006
    ..g., Southern blotting, fluorescence in situ hybridization (FISH), quantitative PCR (qPCR), and breakpoint PCR, they have some clear advantages, including high resolution, high throughput, amenability to multiplexing, and simplicity...
  39. pmc mRNA degradation controls differentiation state-dependent differences in transcript and splice variant abundance
    Peter A C 't Hoen
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Nucleic Acids Res 39:556-66. 2011
    ..In conclusion, control of stability and degradation emerge as important determinants for differential expression of mRNA transcripts and splice variants...
  40. ncbi request reprint Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations
    Annemieke Aartsma-Rus
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 30:293-9. 2009
    ..Further research is needed to determine the functionality of different in-frame dystrophins and a number of hurdles has to be overcome before this approach can be applied clinically...
  41. ncbi request reprint Preventing formation of toxic N-terminal huntingtin fragments through antisense oligonucleotide-mediated protein modification
    Melvin M Evers
    1 Department of Human Genetics, Leiden University Medical Center, The Netherlands
    Nucleic Acid Ther 24:4-12. 2014
    ..Our proof of concept shows a completely novel approach to reduce mutant huntingtin toxicity not by reducing its expressing levels, but by modifying the huntingtin protein. ..
  42. doi request reprint GPSM2 and Chudley-McCullough syndrome: a Dutch founder variant brought to North America
    Rowida Almomani
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Am J Med Genet A 161:973-6. 2013
    ..Since the c.1473delG variant was found in Mennonite settlers, it likely originated in Europe. To support DNA diagnostics, we established an LOVD database for GPSM2 containing all variants thus far described...
  43. doi request reprint Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome
    Gijs W E Santen
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Nat Genet 44:379-80. 2012
    ....
  44. doi request reprint Curating gene variant databases (LSDBs): toward a universal standard
    Jacopo Celli
    Human and Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands
    Hum Mutat 33:291-7. 2012
    ..Our overview is a first step toward establishing overall guidelines for database curation and ultimately covers one aspect of establishing quality-assured gene variant databases...
  45. ncbi request reprint LOVD: easy creation of a locus-specific sequence variation database using an "LSDB-in-a-box" approach
    Ivo F A C Fokkema
    Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 26:63-8. 2005
    ..The LOVD software is freely available from the Leiden Muscular Dystrophy pages (www.DMD.nl/LOVD/). To promote the use of LOVD, we currently offer curators the possibility to set up an LSDB on our Leiden server...
  46. pmc Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase
    Saskia A J Lesnik Oberstein
    Center for Human and Clinical Genetics, Department of Clinical Genetics, K5 R, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Am J Hum Genet 79:562-6. 2006
    ..This finding is expected to put Peters Plus syndrome on the growing list of congenital malformation syndromes caused by glycosylation defects...
  47. ncbi request reprint Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker
    Martin Wildeman
    Department of Human Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 29:6-13. 2008
    ..Mutalyzer will be linked to the Leiden Open source Variation Database (LOVD) (www.LOVD.nl; last accessed 13 September 2007) and is the first module of a sequence variant effect prediction package...
  48. pmc Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease
    Willeke M C van Roon-Mom
    Center for Human and Clinical Genetics, Leiden, The Netherlands
    BMC Mol Biol 9:84. 2008
    ..mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease...
  49. pmc New methods for next generation sequencing based microRNA expression profiling
    Henk P J Buermans
    Center for Human and Clinical Genetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The Netherlands
    BMC Genomics 11:716. 2010
    ..A modification to the small-RNA expression kit (SREK, Ambion) library preparation method for the SOLiD sequencing platform is described to generate microRNA sequencing libraries that are compatible with the Illumina Genome Analyzer...
  50. doi request reprint DMD transcript imbalance determines dystrophin levels
    Pietro Spitali
    1Department of Human Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    FASEB J 27:4909-16. 2013
    ..We suggest that the availability of the complete transcript is a key factor to determine protein abundance and thus will influence the outcome of mRNA-targeting therapies...
  51. doi request reprint Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by variants in TPP1, the gene involved in classic late-infantile neuronal ceroid lipofuscinosis 2 disease (CLN2 disease)
    Yu Sun
    Center for Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    Hum Mutat 34:706-13. 2013
    ....
  52. ncbi request reprint Copy number variation in regions flanked (or unflanked) by duplicons among patients with developmental delay and/or congenital malformations; detection of reciprocal and partial Williams-Beuren duplications
    Marjolein Kriek
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Hum Genet 14:180-9. 2006
    ..11. Our results support the hypothesis that regions flanked by duplicons are enriched for copy number variations...
  53. doi request reprint Successful long-term growth hormone therapy in a girl with haploinsufficiency of the insulin-like growth factor-I receptor due to a terminal 15q26.2->qter deletion detected by multiplex ligation probe amplification
    Marie J E Walenkamp
    Department of Pediatrics J6 S, Leiden University Medical Center, Leiden, The Netherlands
    J Clin Endocrinol Metab 93:2421-5. 2008
    ..The incidence of submicroscopic deletions is unknown, as is the effect of GH therapy in this condition...
  54. pmc Tissue-specific transcript annotation and expression profiling with complementary next-generation sequencing technologies
    Matthew S Hestand
    The Center for Human and Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Nucleic Acids Res 38:e165. 2010
    ..Next-generation sequencing of CAGE and SAGE libraries provides consistent expression levels and can enrich current genome annotations with tissue-specific promoters and alternative 3'-UTR usage...
  55. ncbi request reprint Sarcoglycanopathies and the risk of undetected deletion alleles in diagnosis
    Stefan J White
    Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 26:59. 2005
    ....
  56. ncbi request reprint Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule
    Annemieke Aartsma-Rus
    Leiden University Medical Center, Department of Human Genetics, P O Box 9600, 2300 RC Leiden, The Netherlands
    Muscle Nerve 34:135-44. 2006
    ..In this study we provide an update of the mutational variability in the DMD gene, particularly focusing on genotype-phenotype correlations and mutations that appear to be exceptions to the reading-frame rule...
  57. pmc Microarray retriever: a web-based tool for searching and large scale retrieval of public microarray data
    Alexander E Ivliev
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Nucleic Acids Res 36:W327-31. 2008
    ..The tool is available on the web at: http://www.lgtc.nl/MaRe/..
  58. pmc Cost-effective HRMA pre-sequence typing of clone libraries; application to phage display selection
    Barry A Pepers
    Center for Human and Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands
    BMC Biotechnol 9:50. 2009
    ..In the current study we show that high-resolution melt curve analysis (HRMA) is a simple, cost-saving tool to quickly study clonal variation without prior nucleotide sequence knowledge...
  59. pmc Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2
    Richard J L F Lemmers
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Nat Genet 44:1370-4. 2012
    ..Our study identifies SMCHD1 as an epigenetic modifier of the D4Z4 metastable epiallele and as a causal genetic determinant of FSHD2 and possibly other human diseases subject to epigenetic regulation...
  60. pmc The effects of low levels of dystrophin on mouse muscle function and pathology
    Maaike van Putten
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 7:e31937. 2012
    ..Based on these findings, we conclude that while even dystrophin levels below 15% can improve pathology and performance, levels of >20% are needed to fully protect muscle fibers from exercise-induced damage...
  61. doi request reprint Single molecule sequencing of free DNA from maternal plasma for noninvasive trisomy 21 detection
    Jessica M E van den Oever
    Center for Human and Clinical Genetics, Laboratory for Diagnostic Genome Analysis, Leiden University Medical Center, Leiden, The Netherlands
    Clin Chem 58:699-706. 2012
    ..To eliminate this bias, and thereby experimental noise, we have used single molecule sequencing as an alternative method...
  62. pmc Increased sensitivity of next generation sequencing-based expression profiling after globin reduction in human blood RNA
    Anastasios Mastrokolias
    Center for Human and Clinical Genetics, Leiden University Medical Center, Einthovenweg 20, 2333ZC, Leiden, The Netherlands
    BMC Genomics 13:28. 2012
    ..We have removed globin transcripts from 6 human whole blood RNA samples with a human globin reduction kit and compared them with the same non-reduced samples using deep Serial Analysis of Gene Expression...
  63. pmc Comprehensive gene-expression survey identifies wif1 as a modulator of cardiomyocyte differentiation
    Henk P J Buermans
    Human and Clinical Genetics Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 5:e15504. 2010
    ..In ovo exposure of the HH12 chicken embryonic heart to Wif1 increases the Tbx18-positive cardiac progenitor pool. These data indicate that Wif1 enhances cardiomyogenesis...
  64. doi request reprint High-throughput genotyping of mannose-binding lectin variants using high-resolution DNA-melting analysis
    Rolf H A M Vossen
    Leiden Genome Technology Center, Human and Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands
    Hum Mutat 31:E1286-93. 2010
    ..The present study thereby facilitates further clinical studies into the role of MBL in inflammatory and infectious disease...
  65. ncbi request reprint Y chromosome detection by Real Time PCR and pyrophosphorolysis-activated polymerisation using free fetal DNA isolated from maternal plasma
    Elles M J Boon
    Leiden University Medical Center, Center for Human and Clinical Genetics, Leiden, The Netherlands
    Prenat Diagn 27:932-7. 2007
    ....
  66. doi request reprint New insights in gene-derived therapy: the example of Duchenne muscular dystrophy
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Ann N Y Acad Sci 1214:199-212. 2010
    ..This review will explain the rationale and current state of affairs of these approaches and will then discuss how these gene-derived therapies might also be applicable to other diseases...
  67. ncbi request reprint Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy
    Annemieke Aartsma-Rus
    Department of Human Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
    Neuromuscul Disord 12:S71-7. 2002
    ..Accordingly, these antisense oligoribonucleotides would allow correction of over 50% of deletions and 22% of duplications reported in the Leiden DMD-mutation Database...
  68. doi request reprint Serum protein profiling in mice: identification of Factor XIIIa as a potential biomarker for muscular dystrophy
    Sharmini Alagaratnam
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Proteomics 8:1552-63. 2008
    ..This work underlines the translational aspect of serum protein profiling in mice and supports a further study with serum from patients with neuromuscular disorders...
  69. ncbi request reprint Two-color multiplex ligation-dependent probe amplification: detecting genomic rearrangements in hereditary multiple exostoses
    Stefan J White
    Center for Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    Hum Mutat 24:86-92. 2004
    ..The approach is especially suited for cases in which the number of patients to be tested is limited, making it financially unattractive to invest in cloning...
  70. pmc Can subtle changes in gene expression be consistently detected with different microarray platforms?
    Paola Pedotti
    Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
    BMC Genomics 9:124. 2008
    ..Here we address the performance and the overlap in the detection of differentially expressed genes for five different microarray platforms in a challenging biological context where differences in gene expression are few and subtle...
  71. pmc Poly(A) binding protein nuclear 1 levels affect alternative polyadenylation
    Eleonora de Klerk
    Center for Human and Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Nucleic Acids Res 40:9089-101. 2012
    ....
  72. doi request reprint Literature-aided interpretation of gene expression data with the weighted global test
    Rob Jelier
    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Brief Bioinform 12:518-29. 2011
    ..Literature mining tools are therefore powerful additions to the toolbox for the interpretation of high-throughput genomics data...
  73. pmc Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease
    Jeroen H Roelfsema
    Center for Human and Clinical Genetics, Leiden University Medical Center, Sylvius Laboratory, Leiden, The Netherlands
    Am J Hum Genet 76:572-80. 2005
    ..We extended the search for mutations to the EP300 gene and showed that mutations in EP300 also cause this disorder. These are the first mutations identified in EP300 for a congenital disorder...
  74. doi request reprint Multiplex PCR for identifying DMD gene deletions
    Johan T den Dunnen
    Leiden University Medical Center, Leiden, The Netherlands
    Curr Protoc Hum Genet . 2006
    ..The Alternate Protocol is a modification of the Basic Protocol for radioactive detection of duplications in males and deletions in carrier females...
  75. doi request reprint Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2
    Emmelien Aten
    Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Nederlands
    Hum Mutat 31:1125-33. 2010
    ..Other missense mutations in MBTPS2 have recently been identified in patients with IFAP syndrome. We postulate that both phenotypes are in the spectrum of one genetic disorder with a partially overlapping phenotype...
  76. pmc GeneHopper: a web-based search engine to link gene-expression platforms through GenBank accession numbers
    B Anders T Svensson
    Center for Human and Clinical Genetics Leiden Genome Technology Center, Leiden University Medical Center, The Netherlands
    Genome Biol 4:R35. 2003
    ..We have developed the web-based search engine GeneHopper to link different expression resources based on UniGene clusters and HomoloGene orthologs databases of the National Center for Biotechnology Information (NCBI)...
  77. doi request reprint Mutation nomenclature
    Johan T den Dunnen
    Leiden University Medical Center, Leiden, The Netherlands
    Curr Protoc Hum Genet . 2003
    ..This unit summarizes these nomenclature recommendations, which stimulated a uniform and unequivocal description of sequence variants in literature...
  78. pmc Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2
    Jessica C de Greef
    Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
    Am J Hum Genet 88:796-804. 2011
    ....
  79. pmc Comprehensive detection of genomic duplications and deletions in the DMD gene, by use of multiplex amplifiable probe hybridization
    Stefan White
    Human and Clinical Genetics, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands
    Am J Hum Genet 71:365-74. 2002
    ..Furthermore, the methodology should be applicable to any genetic disease, it should be easily expandable to cover >200 probes, and its characteristics should facilitate high-throughput screening...
  80. doi request reprint LOVD v.2.0: the next generation in gene variant databases
    Ivo F A C Fokkema
    Center of Human and Clinical Genetics, Department of Human Genetics, Leiden University Medical Center, Leiden, Nederland
    Hum Mutat 32:557-63. 2011
    ..To promote LSDB standardization and thereby database interoperability, we offer free server space and help to establish an LSDB on our Leiden server...
  81. doi request reprint High-resolution melting analysis (HRMA): more than just sequence variant screening
    Rolf H A M Vossen
    Leiden Genome Technology Center LGTC, Human and Clincal Genetics, Leiden University Medical Center, Leiden, The Netherlands
    Hum Mutat 30:860-6. 2009
    ..Together, these diverse applications make HRMA a multipurpose technology and a standard tool that should be present in any laboratory studying nucleic acids...