Joris A Veltman

Summary

Affiliation: Radboud University Nijmegen Medical Centre
Country: The Netherlands

Publications

  1. pmc Genome-wide copy number profiling on high-density bacterial artificial chromosomes, single-nucleotide polymorphisms, and oligonucleotide microarrays: a platform comparison based on statistical power analysis
    Jayne Y Hehir-Kwa
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    DNA Res 14:1-11. 2007
  2. pmc Accurate distinction of pathogenic from benign CNVs in mental retardation
    Jayne Y Hehir-Kwa
    Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen, The Netherlands
    PLoS Comput Biol 6:e1000752. 2010
  3. pmc Forging links between human mental retardation-associated CNVs and mouse gene knockout models
    Caleb Webber
    MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    PLoS Genet 5:e1000531. 2009
  4. pmc Pyrosequencing of 16S rRNA gene amplicons to study the microbiota in the gastrointestinal tract of carp (Cyprinus carpio L.)
    Maartje Ahj van Kessel
    Department of Microbiology, IWWR, Radboud University Nijmegen, Heyendaalseweg 135, NL 6525 AJ Nijmegen, The Netherlands
    AMB Express 1:41. 2011
  5. pmc Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies
    L E L M Vissers
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, P O Box 9101, 6500 HB Nijmegen, The Netherlands
    Hum Genet 121:697-709. 2007
  6. pmc Diagnostic genome profiling: unbiased whole genome or targeted analysis?
    Joris A Veltman
    Department of Human Genetics 855, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    J Mol Diagn 8:534-7; discussion 537-9. 2006
  7. pmc Definition of a critical region on chromosome 18 for congenital aural atresia by arrayCGH
    Joris A Veltman
    Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands
    Am J Hum Genet 72:1578-84. 2003
  8. ncbi request reprint Genomic microarrays in clinical diagnosis
    Joris A Veltman
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Curr Opin Pediatr 18:598-603. 2006
  9. ncbi request reprint Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing
    Janneke H M Schuurs-Hoeijmakers
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    J Med Genet 50:802-11. 2013
  10. ncbi request reprint Interstitial 2.2 Mb deletion at 9q34 in a patient with mental retardation but without classical features of the 9q subtelomeric deletion syndrome
    Tjitske Kleefstra
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands
    Am J Med Genet A 140:618-23. 2006

Detail Information

Publications96

  1. pmc Genome-wide copy number profiling on high-density bacterial artificial chromosomes, single-nucleotide polymorphisms, and oligonucleotide microarrays: a platform comparison based on statistical power analysis
    Jayne Y Hehir-Kwa
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    DNA Res 14:1-11. 2007
    ..These analyses provide a first objective insight into the true capacities and limitations of different genomic microarrays to detect and define DNA copy-number variations...
  2. pmc Accurate distinction of pathogenic from benign CNVs in mental retardation
    Jayne Y Hehir-Kwa
    Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen, The Netherlands
    PLoS Comput Biol 6:e1000752. 2010
    ..These results indicate that this classification method will be of value for objectively prioritizing CNVs in clinical research and diagnostics...
  3. pmc Forging links between human mental retardation-associated CNVs and mouse gene knockout models
    Caleb Webber
    MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    PLoS Genet 5:e1000531. 2009
    ..This study is the first to demonstrate how the power of mouse knockout data can be systematically exploited to better understand genetically heterogeneous neurological disorders...
  4. pmc Pyrosequencing of 16S rRNA gene amplicons to study the microbiota in the gastrointestinal tract of carp (Cyprinus carpio L.)
    Maartje Ahj van Kessel
    Department of Microbiology, IWWR, Radboud University Nijmegen, Heyendaalseweg 135, NL 6525 AJ Nijmegen, The Netherlands
    AMB Express 1:41. 2011
    ..Many of these bacteria might be of high physiological relevance for carp as these groups have been implicated in vitamin production, nitrogen cycling and (cellulose) fermentation...
  5. pmc Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies
    L E L M Vissers
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, P O Box 9101, 6500 HB Nijmegen, The Netherlands
    Hum Genet 121:697-709. 2007
    ..Our findings suggest that the LCR burden in proximal 17p may have stimulated the formation of these CCRs and, thus, that genome architectural features such as LCRs may have been instrumental in the generation of these CCRs...
  6. pmc Diagnostic genome profiling: unbiased whole genome or targeted analysis?
    Joris A Veltman
    Department of Human Genetics 855, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    J Mol Diagn 8:534-7; discussion 537-9. 2006
  7. pmc Definition of a critical region on chromosome 18 for congenital aural atresia by arrayCGH
    Joris A Veltman
    Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands
    Am J Hum Genet 72:1578-84. 2003
    ..Deletion and amplification mapping can now be performed at the submicroscopic level and will allow high-throughput definition of genomic regions harboring disease genes...
  8. ncbi request reprint Genomic microarrays in clinical diagnosis
    Joris A Veltman
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Curr Opin Pediatr 18:598-603. 2006
    ..This review describes the various genomic microarray approaches that have been developed for molecular cytogenetic purposes and their implementation in a routine clinical diagnostic setting...
  9. ncbi request reprint Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing
    Janneke H M Schuurs-Hoeijmakers
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    J Med Genet 50:802-11. 2013
    ..Mutations in more than 10% of all human genes are considered to be involved in this disorder, although the majority of these genes are still unknown...
  10. ncbi request reprint Interstitial 2.2 Mb deletion at 9q34 in a patient with mental retardation but without classical features of the 9q subtelomeric deletion syndrome
    Tjitske Kleefstra
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands
    Am J Med Genet A 140:618-23. 2006
    ..Moreover, it confirms the importance of the Eu-HMTase1 gene as the major causative factor of the classical 9qter syndrome phenotype...
  11. ncbi request reprint Genotype-phenotype mapping of chromosome 18q deletions by high-resolution array CGH: an update of the phenotypic map
    Ilse Feenstra
    Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen, The Netherlands
    Am J Med Genet A 143:1858-67. 2007
    ..3 Mb located within 18q22.3-q23. Molecular characterization of more patients will ultimately lead to a further delineation of the critical regions and thus to the identification of candidate genes for these specific traits...
  12. ncbi request reprint A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism
    David A Koolen
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
    Nat Genet 38:999-1001. 2006
    ..The deletions encompass the MAPT and CRHR1 genes and are associated with a common inversion polymorphism...
  13. pmc A compound heterozygous mutation in DPAGT1 results in a congenital disorder of glycosylation with a relatively mild phenotype
    Zafar Iqbal
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Eur J Hum Genet 21:844-9. 2013
    ..Our results show that the clinical spectrum of DPAGT1-CDG is much broader than appreciated so far. ..
  14. doi request reprint Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation
    Dorien Lugtenberg
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Am J Med Genet A 152:638-45. 2010
    ..9-fold lower frequency of ZNF630 duplications was observed in patients, which was not significant either (P-value = 0.163). These data do not show that ZNF630 deletions or duplications are associated with mental retardation...
  15. ncbi request reprint Genomic microarrays in mental retardation: a practical workflow for diagnostic applications
    David A Koolen
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Hum Mutat 30:283-92. 2009
    ..2% (71.9% losses, 19.6% gains, 8.5% complex) could be identified, reflecting the overall diagnostic yield of clinically significant CNVs in individuals with unexplained mental retardation...
  16. doi request reprint Massively parallel sequencing of ataxia genes after array-based enrichment
    Alexander Hoischen
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Hum Mutat 31:494-9. 2010
    ..We conclude that massive parallel sequencing of enriched samples enables personalized diagnosis of heterogeneous genetic disorders and qualifies for rapid diagnostic implementation...
  17. pmc Diagnostic genome profiling in mental retardation
    Bert B A de Vries
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Am J Hum Genet 77:606-16. 2005
    ..Our results indicate that the diagnostic yield of this approach in the general population of patients with MR is at least twice as high as that of standard GTG-banded karyotyping...
  18. doi request reprint GATAD2B loss-of-function mutations cause a recognisable syndrome with intellectual disability and are associated with learning deficits and synaptic undergrowth in Drosophila
    Marjolein H Willemsen
    Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands
    J Med Genet 50:507-14. 2013
    ..We recently identified two de novo loss-of-function mutations in GATAD2B by whole exome sequencing in two unrelated individuals with severe intellectual disability...
  19. pmc ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature
    Rob W J Collin
    Department of Human Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands
    Proc Natl Acad Sci U S A 110:9856-61. 2013
    ..His455Tyr mutant ZNF408. Together, our data strongly suggest that mutant ZNF408 results in abnormal retinal vasculogenesis in humans and is associated with FEVR...
  20. pmc Recurrent de novo mutations in PACS1 cause defective cranial-neural-crest migration and define a recognizable intellectual-disability syndrome
    Janneke H M Schuurs-Hoeijmakers
    Department of Human Genetics 855, Nijmegen Centre for Molecular Life Sciences and Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    Am J Hum Genet 91:1122-7. 2012
    ..Our findings suggest that PACS1 is necessary for the formation of craniofacial structures and that perturbation of its functions results in a specific syndromic ID phenotype...
  21. doi request reprint Targeted next generation sequencing reveals a novel intragenic deletion of the TPO gene in a family with intellectual disability
    Zafar Iqbal
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands
    Arch Med Res 43:312-6. 2012
    ..In the present study we investigated a consanguineous Pakistani family with intellectual disability (ID)...
  22. pmc Disruption of teashirt zinc finger homeobox 1 is associated with congenital aural atresia in humans
    Ilse Feenstra
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Am J Hum Genet 89:813-9. 2011
    ..Trp241X) and c.946_947delinsA (p.Pro316ThrfsX16), and both mutations predicted a loss of function. Together, these results demonstrate that hemizygosity of TSHZ1 leads to congenital aural atresia as a result of haploinsufficiency...
  23. doi request reprint Clinical and cytogenetic characterization of 13 Dutch patients with deletion 9p syndrome: Delineation of the critical region for a consensus phenotype
    Marielle E M Swinkels
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen Centre of Molecular Life Sciences, Nijmegen, The Netherlands
    Am J Med Genet A 146:1430-8. 2008
    ..Sequence analysis of this gene in nine additional patients with isolated trigonocephaly did not reveal any pathogenic mutations...
  24. doi request reprint A de novo paradigm for mental retardation
    Lisenka E L M Vissers
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nat Genet 42:1109-12. 2010
    ..Together with de novo copy number variation, de novo point mutations of large effect could explain the majority of all mental retardation cases in the population...
  25. pmc Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome
    Christian Gilissen
    Department of Human Genetics, Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, The Netherlands
    Am J Hum Genet 87:418-23. 2010
    ..WDR35 is homologous to TULP4 (from the Tubby superfamily) and has previously been characterized as an intraflagellar transport component, confirming that Sensenbrenner syndrome is a ciliary disorder...
  26. ncbi request reprint A novel 2.3 Mb microduplication of 12q24.21q24.23 detected by genome-wide tiling-path resolution array comparative genomic hybridization in a girl with syndromic mental retardation
    Mariken Ruiter
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Clin Dysmorphol 15:133-7. 2006
    ..The current case shows that microduplications might be a more frequent cause of mental retardation and human malformation than previously appreciated...
  27. pmc Next-generation genetic testing for retinitis pigmentosa
    Kornelia Neveling
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Hum Mutat 33:963-72. 2012
    ..De novo dominant mutations appear to play a significant role in patients with isolated RP, having major implications for genetic counselling...
  28. doi request reprint De novo copy number variants associated with intellectual disability have a paternal origin and age bias
    Jayne Y Hehir-Kwa
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    J Med Genet 48:776-8. 2011
    ..Insight into the genomic and environmental factors predisposing to the generation of these de novo events is therefore of significant clinical importance...
  29. pmc Next-generation sequencing of a 40 Mb linkage interval reveals TSPAN12 mutations in patients with familial exudative vitreoretinopathy
    Konstantinos Nikopoulos
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Am J Hum Genet 86:240-7. 2010
    ..Furthermore, we demonstrate the power of targeted next-generation sequencing technology to identify disease genes in linkage intervals...
  30. doi request reprint Rare pathogenic microdeletions and tandem duplications are microhomology-mediated and stimulated by local genomic architecture
    Lisenka E L M Vissers
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Hum Mol Genet 18:3579-93. 2009
    ..These data suggest that rare pathogenic microdeletions and tandem duplications do not occur at random genome sequences, but are stimulated and potentially catalyzed by various genomic architectural features...
  31. ncbi request reprint Identification of disease genes by whole genome CGH arrays
    Lisenka E L M Vissers
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101 6500 HB Nijmegen, The Netherlands
    Hum Mol Genet 14:R215-23. 2005
    ..We expect that, ultimately, genomic copy number scanning of all 250,000 exons in the human genome will enable immediate disease gene discovery in cases exhibiting single exon duplications and/or deletions...
  32. pmc Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy
    Kornelia Neveling
    Department of Human Genetics, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands Institute for Genetic and Metabolic Disease, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
    Am J Hum Genet 92:946-54. 2013
    ..These data emphasize the relevance of BICD2 in synaptic-vesicle recycling and support the conclusion that BICD2 mutations cause congenital slowly progressive dominant SMA...
  33. doi request reprint A mutation in the FAM36A gene, the human ortholog of COX20, impairs cytochrome c oxidase assembly and is associated with ataxia and muscle hypotonia
    Radek Szklarczyk
    Centre for Molecular and Biomolecular Informatics, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen 6500HB, The Netherlands
    Hum Mol Genet 22:656-67. 2013
    ..These results establish the function of the human gene FAM36A/COX20 in complex IV assembly and support a causal role of the gene in complex IV deficiency...
  34. doi request reprint Genomic microarrays in mental retardation: from copy number variation to gene, from research to diagnosis
    Lisenka E L M Vissers
    Department of Human Genetics 855, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen 6500 HB, The Netherlands
    J Med Genet 47:289-97. 2010
    ..In addition, a future prospect is provided for the detection of disease causing mutations and structural variants by next generation sequencing technologies...
  35. ncbi request reprint De novo mutations of SETBP1 cause Schinzel-Giedion syndrome
    Alexander Hoischen
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nat Genet 42:483-5. 2010
    ..We also identified SETBP1 mutations in eight additional cases using Sanger sequencing. All mutations clustered to a highly conserved 11-bp exonic region, suggesting a dominant-negative or gain-of-function effect...
  36. doi request reprint De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome
    Alexander Hoischen
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nat Genet 43:729-31. 2011
    ..In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous...
  37. ncbi request reprint Holoprosencephaly and preaxial polydactyly associated with a 1.24 Mb duplication encompassing FBXW11 at 5q35.1
    David A Koolen
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, 9101, 6500 HB, Nijmegen, The Netherlands
    J Hum Genet 51:721-6. 2006
    ..Additional research is needed to further establish the role of genes from the 5q35.1 region in brain and limb development and to determine the prevalence of copy number gain in the 5q35.1 region among HPE patients...
  38. pmc Homozygosity mapping in outbred families with mental retardation
    Janneke H M Schuurs-Hoeijmakers
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Eur J Hum Genet 19:597-601. 2011
    ..9 Mb (98 genes) in common with the 5.4 Mb MRT11 locus (195 genes). These data support that homozygosity mapping in outbred families may contribute to identification of novel AR-MR genes...
  39. pmc Recurrent CNVs disrupt three candidate genes in schizophrenia patients
    Terry Vrijenhoek
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
    Am J Hum Genet 83:504-10. 2008
    ..Our study supports a role for rare CNVs in schizophrenia susceptibility and identifies at least three candidate genes for this complex disorder...
  40. pmc High-throughput analysis of subtelomeric chromosome rearrangements by use of array-based comparative genomic hybridization
    Joris A Veltman
    Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands
    Am J Hum Genet 70:1269-76. 2002
    ..The robustness and simplicity of this array-based telomere copy-number screening make it highly suited for introduction into the clinic as a rapid and sensitive automated diagnostic procedure...
  41. ncbi request reprint A post-hoc comparison of the utility of sanger sequencing and exome sequencing for the diagnosis of heterogeneous diseases
    Kornelia Neveling
    Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands Institute for Genetic and Metabolic Disease, Radboud University Medical Centre, Nijmegen, The Netherlands
    Hum Mutat 34:1721-6. 2013
    ..Even if all genes that could have been ordered by physicians had been tested, the larger number of genes captured by the exome would still have led to a clearly superior diagnostic yield at a fraction of the cost. ..
  42. ncbi request reprint Mutations in a new member of the chromodomain gene family cause CHARGE syndrome
    Lisenka E L M Vissers
    Department of Human Genetics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    Nat Genet 36:955-7. 2004
    ..Sequence analysis of genes located in this region detected mutations in the gene CHD7 in 10 of 17 individuals with CHARGE syndrome without microdeletions, accounting for the disease in most affected individuals...
  43. doi request reprint Diagnostic exome sequencing in persons with severe intellectual disability
    Joep de Ligt
    Department of Human Genetics, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    N Engl J Med 367:1921-9. 2012
    ..The causes of intellectual disability remain largely unknown because of extensive clinical and genetic heterogeneity...
  44. pmc STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis
    Sanne P Smeekens
    Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    PLoS ONE 6:e29248. 2011
    ..The challenge for the future is to translate this knowledge into novel strategies for the treatment of this severe immunodeficiency...
  45. ncbi request reprint Identification of novel mutations in patients with Leber congenital amaurosis and juvenile RP by genome-wide homozygosity mapping with SNP microarrays
    Anneke I den Hollander
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Invest Ophthalmol Vis Sci 48:5690-8. 2007
    ..Thus far, mutations in 13 genes have been associated with autosomal recessive LCA and juvenile RP. The purpose of this study was to use homozygosity mapping to identify mutations in known LCA and juvenile RP genes...
  46. doi request reprint Association of the Alzheimer's gene SORL1 with hippocampal volume in young, healthy adults
    Janita Bralten
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands
    Am J Psychiatry 168:1083-9. 2011
    ....
  47. pmc Array-based comparative genomic hybridization for the genomewide detection of submicroscopic chromosomal abnormalities
    Lisenka E L M Vissers
    Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands
    Am J Hum Genet 73:1261-70. 2003
    ..This high-resolution assay will facilitate the identification of novel genes involved in human mental retardation and/or malformation syndromes and will provide insight into the flexibility and plasticity of the human genome...
  48. doi request reprint Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders
    Zafar Iqbal
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Donders Institute for Brain, Cognitionand Behaviour, Radboud University Medical Centre, Nijmegen, TheNetherlands
    Hum Mol Genet 22:1960-70. 2013
    ..In addition, our findings support the suggested association of ANK3 with various neuropsychiatric disorders and illustrate the genetic and molecular relation between a wide range of neurodevelopmental disorders...
  49. ncbi request reprint Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation
    David A Koolen
    1Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Eur J Hum Genet 13:1019-24. 2005
    ....
  50. pmc Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability
    Tjitske Kleefstra
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands
    Am J Hum Genet 91:73-82. 2012
    ..We propose a highly conserved epigenetic network that underlies cognition in health and disease. This network should allow the design of strategies to treat the growing group of ID pathologies that are caused by epigenetic defects...
  51. ncbi request reprint Diagnostic serum glycosylation profile in patients with intellectual disability as a result of MAN1B1 deficiency
    Monique van Scherpenzeel
    1 Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
    Brain 137:1030-8. 2014
    ..In addition, it provides a functional confirmation of MAN1B1 mutations as identified by next-generation sequencing in individuals with intellectual disability. ..
  52. pmc Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis
    Wybrich R Cnossen
    Departments of Gastroenterology and Hepatology and Human Genetics and Center for Molecular and Biomolecular Informatics, Institute for Genetic and Metabolic Disease, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands
    Proc Natl Acad Sci U S A 111:5343-8. 2014
    ..The findings presented in this study link the pathophysiology of PCLD to deregulation of the canonical wingless signaling pathway. ..
  53. pmc Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems
    Anneke T Vulto-van Silfhout
    Department of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands
    Am J Hum Genet 94:649-61. 2014
    ..Our results demonstrate that mutations in DEAF1 cause ID and behavioral problems, most likely as a result of impaired transcriptional regulation by DEAF1. ..
  54. pmc Unlocking Mendelian disease using exome sequencing
    Christian Gilissen
    Department of Human Genetics, Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
    Genome Biol 12:228. 2011
    ..Exome sequencing is revolutionizing Mendelian disease gene identification. This results in improved clinical diagnosis, more accurate genotype-phenotype correlations and new insights into the role of rare genomic variation in disease...
  55. pmc Mutations in DDHD2, encoding an intracellular phospholipase A(1), cause a recessive form of complex hereditary spastic paraplegia
    Janneke H M Schuurs-Hoeijmakers
    Department of Human Genetics 855, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    Am J Hum Genet 91:1073-81. 2012
    ..We show that mutations in DDHD2 cause a specific complex HSP subtype (SPG54), thereby linking a member of the PLA(1) family to human neurologic disease...
  56. doi request reprint Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects
    Marjolein H Willemsen
    Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen, The Netherlands
    J Med Genet 49:179-83. 2012
    ..Furthermore, it interacts with the LIS1 gene of which haploinsufficiency causes a severe neuronal migration disorder in humans, known as classical lissencephaly or Miller-Dieker syndrome...
  57. doi request reprint Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome
    David A Koolen
    Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Nat Genet 44:639-41. 2012
    ..RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes...
  58. doi request reprint Analysis of genes regulated by the transcription factor LUMAN identifies ApoA4 as a target gene in dendritic cells
    Anna Sanecka
    Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Mol Immunol 50:66-73. 2012
    ..Subsequent validation experiments, bioinformatics-based promoter analysis, and silencing studies confirmed that ApoA4 is a true target gene of LUMAN in bone marrow-derived DCs (BMDCs)...
  59. pmc Heterozygous mutations of FREM1 are associated with an increased risk of isolated metopic craniosynostosis in humans and mice
    Lisenka E L M Vissers
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    PLoS Genet 7:e1002278. 2011
    ..Furthermore, we present Frem1 mutant mice as the first bona fide mouse model of human metopic craniosynostosis and a new model for midfacial hypoplasia...
  60. ncbi request reprint Chromosomal breakpoint mapping by arrayCGH using flow-sorted chromosomes
    Imke M Veltman
    Department of Human Genetics, 417, University Medical Center Nijmegen, P O Box 9101, 6500 HB Nijmegen, The Netherlands
    Biotechniques 35:1066-70. 2003
    ..In addition, we have tested the minimal amount of material necessary to perform these experiments and show that it is possible to obtain highly reliable profiles using as little as 10,000 flow-sorted chromosomes...
  61. ncbi request reprint Genomic copy number analysis in mental retardation: finding the needles in the haystack
    Joris A Veltman
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen 6500 HB, The Netherlands
    Eur J Hum Genet 15:1-2. 2007
  62. ncbi request reprint High-resolution genomic microarrays for X-linked mental retardation
    Dorien Lugtenberg
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Genet Med 9:560-5. 2007
    ..In this review, we describe the developments in this field and specifically highlight the impact of these microarray studies in the field of X-linked mental retardation...
  63. pmc Disease gene identification strategies for exome sequencing
    Christian Gilissen
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Eur J Hum Genet 20:490-7. 2012
    ..Exome sequencing is likely to become the most commonly used tool for Mendelian disease gene identification for the coming years...
  64. pmc Cantú syndrome is caused by mutations in ABCC9
    Bregje W M van Bon
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, The Netherlands
    Am J Hum Genet 90:1094-101. 2012
    ..These findings identify the genetic basis of Cantú syndrome and suggest that this is a new member of the potassium channelopathies...
  65. doi request reprint Structural genomic variation in intellectual disability
    Rolph Pfundt
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Methods Mol Biol 838:77-95. 2012
    ..In addition, a detailed protocol is provided for the diagnostic interpretation of copy-number variations in mental retardation...
  66. doi request reprint Functional differences between mesenchymal stem cell populations are reflected by their transcriptome
    Bastiaan J H Jansen
    Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Stem Cells Dev 19:481-90. 2010
    ..Furthermore, these differences indicate a demand for effective differentiation protocols tailored to each stem cell type...
  67. pmc Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal-recessive nonsyndromic hearing impairment
    Margit Schraders
    Department of Otorhinolaryngology, Head and Neck Surgery, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Radboud University Nijmegen, Nijmegen, The Netherlands
    Am J Hum Genet 86:138-47. 2010
    ..Quantitative analysis of GRXCR1 transcripts in fetal and adult human tissues revealed a preferential expression of the gene in fetal cochlea, which may explain the nonsyndromic nature of the hearing impairment...
  68. doi request reprint High density gene expression microarrays and gene ontology analysis for identifying processes in implanted tissue engineering constructs
    Gerwen Lammers
    Department of Biochemistry 280, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, P O Box 9101, 6500 HB Nijmegen, The Netherlands
    Biomaterials 31:8299-312. 2010
    ..However, challenges remain e.g. with regards to the development of specific GO-terms and annotation of the (rat) genome...
  69. pmc The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype
    Bregje W M van Bon
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Eur J Hum Genet 18:163-70. 2010
    ..1 microdeletion present with a variable phenotype and the diagnosis should be considered in mentally retarded children with coarse facies, seizures, disturbed sleeping patterns and additional specific behavioural problems...
  70. pmc Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar Syndrome
    Zafar Iqbal
    Department of Human Genetics 855, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Am J Hum Genet 86:254-61. 2010
    ..Interestingly however, dermal fibroblasts from one of the individuals without an SH3PXD2B mutation nevertheless expressed lower levels of the TKS4 protein, suggesting a common mechanism underlying disease causation...
  71. pmc Chondrodysplasia and abnormal joint development associated with mutations in IMPAD1, encoding the Golgi-resident nucleotide phosphatase, gPAPP
    Lisenka E L M Vissers
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Am J Hum Genet 88:608-15. 2011
    ....
  72. pmc OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5-encoded lebercilin
    Karlien L M Coene
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, The Netherlands
    Am J Hum Genet 85:465-81. 2009
    ..These findings offer a molecular explanation for the phenotypic spectrum observed for OFD1 mutations; this spectrum now includes OFD1 syndrome, SGBS2, and JS...
  73. ncbi request reprint Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis
    Anneke I den Hollander
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nat Genet 39:889-95. 2007
    ..Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA...
  74. doi request reprint Mutations in the phospholipid remodeling gene SERAC1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness
    Saskia B Wortmann
    Department of Pediatrics, Radboud University Nijmegen Medical Centre RUNMC, Nijmegen, The Netherlands
    Nat Genet 44:797-802. 2012
    ..Our data identify SERAC1 as a key player in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking...
  75. doi request reprint De novo mutations in human genetic disease
    Joris A Veltman
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Center, PO Box 9101, Nijmegen, The Netherlands
    Nat Rev Genet 13:565-75. 2012
    ..These mutations, although individually rare, may capture a significant part of the heritability for complex genetic diseases that is not detectable by genome-wide association studies...
  76. pmc Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis
    Erik J M Toonen
    Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    PLoS ONE 7:e33199. 2012
    ..Our results confirm that gene expression profiling prior to treatment is a useful tool to predict anti-TNF (non) response...
  77. pmc Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan
    Tony Roscioli
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nat Genet 44:581-5. 2012
    ..These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates...
  78. pmc Mutations in C8orf37, encoding a ciliary protein, are associated with autosomal-recessive retinal dystrophies with early macular involvement
    Alejandro Estrada-Cuzcano
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, The Netherlands
    Am J Hum Genet 90:102-9. 2012
    ..The two CRD siblings with the c.156-2A>G mutation also showed unilateral postaxial polydactyly. These results underline the importance of disrupted ciliary processes in the pathogenesis of retinal dystrophies...
  79. doi request reprint Common variants in DGKK are strongly associated with risk of hypospadias
    Loes F M van der Zanden
    Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nat Genet 43:48-50. 2011
    ..Expression studies showed expression of DGKK in preputial tissue of cases and controls, which was lower in carriers of the risk allele of rs1934179 (P = 0.047). We propose DGKK as a major risk gene for hypospadias...
  80. doi request reprint Genetic variation in CACNA1C, a gene associated with bipolar disorder, influences brainstem rather than gray matter volume in healthy individuals
    Barbara Franke
    Department of Human Genetics, Institute for Genetic and Metabolic Disorders, Center for Neuroscience, Radboud University Nijmegen Medical Center, The Netherlands
    Biol Psychiatry 68:586-8. 2010
    ..To elucidate the mechanisms by which such effects on psychiatric disease are brought about by genetic factors, we investigated the influence of CACNA1C polymorphisms on brain structure...
  81. doi request reprint STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis
    Frank L van de Veerdonk
    Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    N Engl J Med 365:54-61. 2011
    ..Patients with recessive CMC and autoimmunity have mutations in the autoimmune regulator AIRE. The cause of autosomal dominant CMC is unknown...
  82. doi request reprint Whole-exome sequencing detects somatic mutations of IDH1 in metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA)
    Lisenka E L M Vissers
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Nijmegen, Netherlands
    Am J Med Genet A 155:2609-16. 2011
    ..Thus, somatic mutations in IDH1 may explain all features of MC-HGA, including sporadic occurrence, metaphyseal disorganization, and chondromatosis, urinary excretion of D-2-hydroxy-glutaric acid, and reduced cerebral myelinization...
  83. doi request reprint Amplified segment in the 'Down syndrome critical region' on HSA21 shared between Down syndrome and euploid AML-M0 excludes RUNX1, ERG and ETS2
    Claudia Canzonetta
    Centre for Paediatrics, Blizard Institute, Barts and the London Medical School, Queen Mary University of London, London, UK
    Br J Haematol 157:197-200. 2012
    ..Interestingly, the amplified region does not include the oncogenes RUNX1, ETS2 and ERG...
  84. pmc Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus
    Evelyn N Kouwenhoven
    Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    PLoS Genet 6:e1001065. 2010
    ..These data provide a proof-of-concept that the catalogue of p63 binding sites identified in this study may be of relevance to the studies of SHFM and other congenital malformations that resemble the p63-associated phenotypes...
  85. ncbi request reprint Understanding variable expressivity in microdeletion syndromes
    Joris A Veltman
    Joris A Veltman and Han G Brunner are in the Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and the Institute for Genetic and Metabolic Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Nat Genet 42:192-3. 2010
    ..1. The work highlights the complex relationship between genotype and phenotype and provides a model to explain the clinical variability associated with this and other common microdeletion syndromes...
  86. ncbi request reprint Array-based comparative genomic hybridization for genome-wide screening of DNA copy number in bladder tumors
    Joris A Veltman
    Cancer Center, University of California San Francisco, California 94143 0808, USA
    Cancer Res 63:2872-80. 2003
    ....
  87. ncbi request reprint 12p-amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH
    Gaetano Zafarana
    Pathology Laboratory for Exp Patho Oncology, Erasmus MC Erasmus University Medical Center Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
    Oncogene 22:7695-701. 2003
    ..These data support a mechanistic model in which at least two 12p genes, situated at the border regions of the amplicon, are positional candidates capable of actively supporting tumor progression in TGCTs...
  88. ncbi request reprint Loss of a small region around the PTEN locus is a major chromosome 10 alteration in prostate cancer xenografts and cell lines
    Karin G Hermans
    Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam, The Netherlands
    Genes Chromosomes Cancer 39:171-84. 2004
    ..In some of the samples, PTEN inactivation was accompanied by loss of 1 MINPP1 allele, loss of 1 copy, mutation, or low expression of PAPSS2, and most frequently by loss of 1 or 2 copies or low expression of FLJ11218...
  89. ncbi request reprint Chromosome 22q11 deletion and pachygyria characterized by array-based comparative genomic hybridization
    David A Koolen
    Am J Med Genet A 131:322-4. 2004
  90. ncbi request reprint Microarray analyses reveal strong influence of DNA copy number alterations on the transcriptional patterns in pancreatic cancer: implications for the interpretation of genomic amplifications
    Markus Heidenblad
    Department of Clinical Genetics, Lund University Hospital, SE 221 85 Lund, Sweden
    Oncogene 24:1794-801. 2005
    ..The presented findings indicate that more than one putative target gene may be of importance in most pancreatic cancer amplicons...
  91. ncbi request reprint Characterization of a recurrent 15q24 microdeletion syndrome
    Andrew J Sharp
    Department of Genome Sciences, University of Washington School of Medicine, 1705 NE Pacific Street Seattle, WA 98195, USA
    Hum Mol Genet 16:567-72. 2007
    ..Our results define microdeletion of 15q24 as a novel recurrent genomic disorder...
  92. pmc Whole-genome array comparative genome hybridization: the preferred diagnostic choice in postnatal clinical cytogenetics
    Joris A Veltman
    J Mol Diagn 9:277. 2007
  93. ncbi request reprint Ovotestes and XY sex reversal in a female with an interstitial 9q33.3-q34.1 deletion encompassing NR5A1 and LMX1B causing features of Genitopatellar syndrome
    Silke Schlaubitz
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Am J Med Genet A 143:1071-81. 2007
    ..This suggests that the locus 9q33-9q34 can be excluded for GPS and that the presented case is unique in its combination of GPS and NPS features caused by a microdeletion associated with loss of function of LMX1B and NR5A1...
  94. ncbi request reprint Genome-wide array-based comparative genomic hybridization reveals multiple amplification targets and novel homozygous deletions in pancreatic carcinoma cell lines
    Markus Heidenblad
    Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
    Cancer Res 64:3052-9. 2004
    ..The described amplification and deletion targets are likely to contain genes important in pancreatic tumorigenesis...
  95. ncbi request reprint Array-based comparative genomic hybridization for the differential diagnosis of renal cell cancer
    Monica Wilhelm
    Cancer Center and Departments of Laboratory Medicine and Urology, University of California San Francisco, San Francisco, California 94143 0808, USA
    Cancer Res 62:957-60. 2002
    ..These results indicate that array-based CGH is capable of diagnosing the vast majority of renal cell carcinomas based on their genetic profiles...
  96. pmc Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes
    Heather C Mefford
    University of Washington School of Medicine, Seattle 98195, USA
    N Engl J Med 359:1685-99. 2008
    ..Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients...