0000000000891230

AUTHOR

Paulien A Terhal

showing 3 related works from this author

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

2016

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub…

Proteomics0301 basic medicineSystems AnalysisDNA Mutational Analysislnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]General Physics and AstronomyDatasets as Topicmethods [Chromatography Affinity]ProteomicsSensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]Chromatography AffinityMass SpectrometryProtein Interaction Mappingtherapy [Ciliopathies]genetics [Ciliopathies]methods [Molecular Targeted Therapy]Molecular Targeted TherapyProtein Interaction MapsMultidisciplinaryCiliumChemistry (all)Qabnormalities [Spine]pathology [Ciliopathies]genetics [Muscle Hypotonia]therapy [Muscle Hypotonia]Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]metabolism [Proteins]isolation & purification [Proteins]physiology [Biological Transport]3. Good healthCell biologyVesicular transport proteinpathology [Dwarfism]metabolism [Cilia]Muscle Hypotoniaddc:500pathology [Muscle Hypotonia]pathology [Spine]genetics [Dwarfism]Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]ScienceDwarfismExocystBiologyArticleGeneral Biochemistry Genetics and Molecular BiologyPhysics and Astronomy (all)03 medical and health sciencesIntraflagellar transportCiliogenesisOrganelleHumansCiliaBiochemistry Genetics and Molecular Biology (all)ProteinsBiological TransportGeneral Chemistrytherapy [Dwarfism]Fibroblastsgenetics [Proteins]CiliopathiesSpinemethods [Protein Interaction Mapping]Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]030104 developmental biologyProteostasisHEK293 Cellsmethods [Proteomics]
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Recessive multiple epiphyseal dysplasia (rMED): phenotype delineation in eighteen homozygotes for DTDST mutation R279W.

2003

Multiple epiphyseal dysplasia (MED) is a generalised skeletal dysplasia that although relatively mild is associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. In the past, the disorder was subdivided into the milder Ribbing type, usually with flattened epiphyses,1 and the more severe Fairbank type with round epiphyses,2 but many cases were not classifiable as clearly either type.3 MED can be caused by mutations in at least six separate genes: COMP ,4–7 collagen IX ( COL9A1 , COL9A2 , and COL9A3 ),8–13 matrilin 3 ( MATN3 ),15 and the sulphate transporter, DTDST ( DTDST/SLC26A2 ). We have previously repor…

AdultMalePathologymedicine.medical_specialtyAdolescentAnion Transport ProteinsGenes RecessiveBiologySLC26A2ArginineOsteochondrodysplasiasShort statureMultiple epiphyseal dysplasiaGeneticsmedicineHumansChildGenetics (clinical)GeneticsAchondrogenesisSulfatesPoint mutationHomozygoteTryptophanChromosome MappingMembrane Transport ProteinsBiological TransportMiddle Agedmedicine.diseasePhenotypeGenetic defects of metabolism [UMCN 5.1]Amino Acid SubstitutionDysplasiaSulfate TransportersMutation (genetic algorithm)MutationMutation testingbiology.proteinFemalemedicine.symptomCarrier ProteinsLetter to JMGJournal of medical genetics
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Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases

2017

The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted…

0301 basic medicineSpondyloepimetaphyseal dysplasiabusiness.industry030105 genetics & hereditymedicine.diseaseBioinformaticsPhenotypeShort stature3. Good health03 medical and health sciencesCatel–Manzke syndromeGeneticsEtiologyMedicineLarsen syndromeJoint dislocationmedicine.symptom10. No inequalitybusinessGenetics (clinical)Exome sequencingClinical Genetics
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