Author
Raoul C.M. Hennekam
Other affiliations: Utrecht University, Academic Medical Center, UCL Institute of Child Health ...read more
Bio: Raoul C.M. Hennekam is an academic researcher from University of Amsterdam. The author has contributed to research in topics: Missense mutation & Exome sequencing. The author has an hindex of 96, co-authored 563 publications receiving 35759 citations. Previous affiliations of Raoul C.M. Hennekam include Utrecht University & Academic Medical Center.
Papers published on a yearly basis
Papers
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TL;DR: It is reported that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth and is important for the establishment of peak bone mass.
2,210 citations
Book•
01 Jan 1976
TL;DR: In this article, the authors present a list of the most common and well known syndromes with craniosynostosis and miscellaneous disorders, as well as associations with unusual facies.
Abstract: Deformations and disruptions Teratogenic agents Chromosomal syndromes I: common and/or well known syndromes Chromosomal syndromes II: unusual variants METABOLIC DISORDERS the mucopolysaccharidoses the oligosaccharidoses and related disorders metabolic disorders and dysmorphic features Syndromes affecting bone I: the osteogenesis imperfectas Syndromes affecting bone II: chondrodysplasias and chondrodystrophies Syndromes affecting bone III: craniotubular bone disorders Syndromes affecting bone IV: other skeletal disorders Proportionate short stature syndromes Overgrowth syndromes and postnatal onset obesity syndromes Hamartoneoplastic syndromes Syndromes affecting the skin and mucosa Syndromes with craniosynostosis I: general aspects and well known syndromes Syndromes with craniosynostosis II: miscellaneous syndromes Syndromes of abnormal craniofacial contour Syndromes affecting the central nervous system Syndromes with contractures BRANCHIAL ARCH AND ORO-ACRAL DISORDERS branchial arch syndromes oromandibular-limb hypogenesis syndromes oro-facial-digital syndromes otopalatal digital syndromes Orofacial clefting syndromes I: general aspects Orofacial clefting syndromes II: common and/or well known syndromes Orofacial clefting syndromes III: other syndromes Orofacial clefting syndromes IV: associations Syndromes with unusual facies I: well known syndromes Syndromes with hypertelorism Syndromes with unusual nasal anomalies Syndromes with unusual ocular anomalies Syndromes with facial fat atrophy Syndromes with unusual facies II: other syndromes Syndromes with gingival-periodontal components Syndromes with unusual dental findings Miscellaneous syndromes I: well known syndromes Miscellaneous syndromes II: other syndromes Appendix.
1,869 citations
TL;DR: It is proposed that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.
Abstract: THE Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with facial abnormalities, broad thumbs, broad big toes and mental retardation as the main clinical features1-3. Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16pl3.3 (refs 4-8). Here we report that all these breakpoints are restricted to a region that contains the gene for the human CREB binding protein (CBP), a nuclear protein participating as a co-activator in cyclic-A IMP-regulated gene expression9-12. We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from point mutations in the CBP gene itself. Because the patients are heterozygous for the mutations, we propose that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.
1,149 citations
University of Washington1, University of Geneva2, Ghent University3, Salisbury University4, University Hospital Southampton NHS Foundation Trust5, Katholieke Universiteit Leuven6, Radboud University Nijmegen7, University of Amsterdam8, University College London9, University of Manchester10, University of Bern11, University of Naples Federico II12, University of Glasgow13, Pompeu Fabra University14, Utrecht University15, University of Oxford16, Wellcome Trust Sanger Institute17, University of Chicago18, Vanderbilt University19, Cold Spring Harbor Laboratory20, Howard Hughes Medical Institute21
TL;DR: Recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease are identified.
Abstract: BACKGROUND: Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients. METHODS: We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons. RESULTS: We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P=1.1x10(-7)). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in nine children with mental retardation or autism spectrum disorder and other variable features (P=0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies. CONCLUSIONS: We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype.
690 citations
TL;DR: Analysis of the p63 gene, a homolog of p53 located in the critical LMS/EEC interval, revealed heterozygous mutations in nine unrelated EEC families that provide a molecular explanation for the dominant character of p63 mutations in EEC syndrome.
684 citations
Cited by
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National Institutes of Health1, University of Chicago2, Duke University3, Harvard University4, University of Oxford5, GlaxoSmithKline6, Johns Hopkins University7, Yale University8, deCODE genetics9, Princeton University10, Howard Hughes Medical Institute11, Washington University in St. Louis12, University of California, Berkeley13, Stanford University14, University of Michigan15, Cornell University16, University of Washington17, University of Queensland18, Vanderbilt University19, North Carolina State University20, QIMR Berghofer Medical Research Institute21
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Abstract: Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
7,797 citations
TL;DR: The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels, and that receptor-ligand specificity and feedback loops help to determine WNT signaling outputs.
Abstract: Tight control of cell-cell communication is essential for the generation of a normally patterned embryo. A critical mediator of key cell-cell signaling events during embryogenesis is the highly conserved Wnt family of secreted proteins. Recent biochemical and genetic analyses have greatly enriched our understanding of how Wnts signal, and the list of canonical Wnt signaling components has exploded. The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels. In addition, receptor-ligand specificity and feedback loops help to determine Wnt signaling outputs. Wnts are required for adult tissue maintenance, and perturbations in Wnt signaling promote both human degenerative diseases and cancer. The next few years are likely to see novel therapeutic reagents aimed at controlling Wnt signaling in order to alleviate these conditions.
5,129 citations
TL;DR: Some key aspects of Wnt/beta-catenin signaling in human diseases including congenital malformations, cancer, and osteoporosis are highlighted, and potential therapeutic implications are discussed.
4,926 citations
TL;DR: An update of the core Wnt/β-catenin signaling pathway is provided, how its various components contribute to disease, and outstanding questions to be addressed in the future are discussed.
4,561 citations
TL;DR: Weighted-nearest neighbor analysis as mentioned in this paper is an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities.
3,369 citations