ArticleJournal of medical genetics2014
Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism.
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Article in Journal of medical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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94 citing papers in PubMed, 168 citations in OpenAlex.
- Global transcriptional disturbances underlie Cornelia de Lange syndrome and related phenotypes.The Journal of clinical investigation · 2015Trial
- Clinical delineation and genotype-phenotype correlation of 84 pediatric patients with Cornelia de Lange syndrome: insights from a single-center Chinese study.European journal of pediatrics · 2026Article
- First Cornelia de Lange Syndrome Type 4 Caused by the Gonadal Mosaicism ofHuman mutation · 2026Article
- Contrasting Relationships Between Anxiety and Intolerance of Uncertainty in Cornelia de Lange and Fragile X Syndromes.Journal of intellectual disability research : JIDR · 2025Article
- Non-Classic Cornelia de Lange Syndrome Due toChildren (Basel, Switzerland) · 2025Review
- Butyrate rescues chlorpyrifos-induced social deficits through inhibition of class I histone deacetylases.bioRxiv : the preprint server for biology · 2025Article
- Ophthalmological findings in Brazilian Cornelia de Lange syndrome patients with NIPBL variants.BMC ophthalmology · 2025Article
- Clinical and Molecular Findings in 17 Patients with Cornelia de Lange Syndrome: Four Novel Variants and anMolecular syndromology · 2025Article
- Unfolding neural diversity: how dynamic three-dimensional genome architecture regulates brain function and disease.Molecular psychiatry · 2025Review
- A Case of Trichorhinophalangeal Syndrome Caused by a Novel Heterozygous Nonsense Mutation in theClinical case reports · 2025Article
- Postzygotic mosaicism in SMC1A and the first reported case of a female with Cornelia de Lange syndrome.Scientific reports · 2025Article
- Whole Genome Sequencing of "Mutation-Negative" Individuals With Cornelia de Lange Syndrome.Human mutation · 2025Article
- Human embryonic genetic mosaicism and its effects on development and disease.Nature reviews. Genetics · 2024Review
- Insights into the ANKRD11 variants and short-stature phenotype through literature review and ClinVar database search.Orphanet journal of rare diseases · 2024Review
- SMC3 contributes to heart development by regulating super-enhancer associated genes.Experimental & molecular medicine · 2024Article
- Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome.Molecular genetics & genomic medicine · 2024Article
- Advancing the Clinical and Molecular Understanding of Cornelia de Lange Syndrome: A Multidisciplinary Pediatric Case Series and Review of the Literature.Journal of clinical medicine · 2024Review
- Assessment of Quality of Life Using the Kidslife Scale in Individuals With Cornelia de Lange Syndrome.Cureus · 2024Article
- Neurobehavioral and developmental profiles: genotype-phenotype correlations in individuals with Cornelia de Lange syndrome.Orphanet journal of rare diseases · 2024Article
- Inhibition of HDAC8 Reduces the Proliferation of Adult Neural Stem Cells in the Subventricular Zone.International journal of molecular sciences · 2024Article
34 more citing papers are in PubMed but not listed here.
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75 authors at 20 institutions in 8 countries.
Morad AnsariMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Gemma PokeMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Quentin FerryVisual Geometry Group, Department of Engineering Science, University of Oxford, Oxford, UK Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Kathleen WilliamsonMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Roland AldridgeMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Alison M MeynertMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Hemant BenganiMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Cheng Yee ChanMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Hülya KayseriliMedical Genetics Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Sahin AvciMedical Genetics Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Raoul C M HennekamDepartment of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Anne K LampeSouth East of Scotland Clinical Genetic Service, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK.
Egbert RedekerDepartment of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Tessa HomfrayMedical Genetics Unit, St George's University of London, London, UK.
Alison RossNorth of Scotland Regional Genetics Service, Clinical Genetics Centre, Aberdeen, UK.
Marie Falkenberg SmelandDepartment of Medical Genetics, University Hospital of Northern Norway, Tromsø, Norway.
Sahar MansourMedical Genetics Unit, St George's University of London, London, UK.ORCID http://orcid.org/0000-0001-8357-1287
Michael J ParkerSheffield Children's Hospital, NHS Foundation Trust, Sheffield, UK.
Jacqueline A CookSheffield Children's Hospital, NHS Foundation Trust, Sheffield, UK.
Miranda SplittNorthern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle upon Tyne, UK.
Richard B FisherNorthern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle upon Tyne, UK.
Alan FryerDepartment of Clinical Genetics, Alder Hay Children's Hospital, Liverpool, UK.
Alex C MageeNorthern Ireland Regional Genetics Service (NIRGS), Belfast City Hospital, Belfast, UK.
Andrew WilkieWeatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Angela BarnicoatClinical Genetics Department, Great Ormond Street Hospital, London, UK.
Angela F BradyNorth West Thames Regional Genetics Service, Kennedy-Galton Centre, North West London Hospitals NHS Trust, Harrow, UK.
Nicola S CooperWest Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, West Midlands, UK.
Catherine MercerWessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
Charu DeshpandeDepartment of Genetics, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Christopher P BennettClinical Genetics, Yorkshire Regional Genetics Service, Leeds, UK.
Daniela T PilzInstitute of Medical Genetics, University Hospital of Wales, Cardiff, UK.
Deborah RuddyDepartment of Genetics, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Deirdre CilliersDepartment of Clinical Genetics, The Churchill Hospital Old Road, Oxford, UK.
Diana S JohnsonSheffield Children's Hospital, NHS Foundation Trust, Sheffield, UK.
Dragana JosifovaDepartment of Genetics, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Elisabeth RosserClinical Genetics Department, Great Ormond Street Hospital, London, UK.
Elizabeth M ThompsonSA Clinical Genetics Service, Women's & Children's Hospital, Adelaide, Australia Department of Paediatrics, University of Adelaide, Adelaide, Australia.
Emma WakelingNorth West Thames Regional Genetics Service, Kennedy-Galton Centre, North West London Hospitals NHS Trust, Harrow, UK.
Esther KinningWest of Scotland Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospital, Glasgow, UK.
Fiona StewartNorthern Ireland Regional Genetics Service (NIRGS), Belfast City Hospital, Belfast, UK.
Frances FlinterDepartment of Genetics, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Katta M GirishaDepartment of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
Helen CoxWest Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, West Midlands, UK.
Helen V FirthDepartment of Medical Genetics, Cambridge University Addenbrooke's Hospital, Cambridge, UK.
Helen KingstonFaculty of Medical and Human Sciences, Manchester Centre for Genomic Medicine, Institute of Human Development, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
Jamie S WeeDepartment of Dermatology, Kingston Hospital NHS Trust, Surrey, UK.
Jane A HurstClinical Genetics Department, Great Ormond Street Hospital, London, UK.
Jill Clayton-SmithFaculty of Medical and Human Sciences, Manchester Centre for Genomic Medicine, Institute of Human Development, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
John TolmieWest of Scotland Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospital, Glasgow, UK.
Julie VogtWest Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital, West Midlands, UK.
Katrina Tatton-BrownMedical Genetics Unit, St George's University of London, London, UK.
Kate ChandlerFaculty of Medical and Human Sciences, Manchester Centre for Genomic Medicine, Institute of Human Development, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
Katrina PrescottClinical Genetics, Yorkshire Regional Genetics Service, Leeds, UK.
Louise WilsonClinical Genetics Department, Great Ormond Street Hospital, London, UK.
Mahdiyeh BehnamMedical Genetics Laboratory of Genome, Isfahan University of Medical Sciences, Isfahan, Iran.
Meriel McEntagartMedical Genetics Unit, St George's University of London, London, UK.
Rosemarie DavidsonWest of Scotland Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospital, Glasgow, UK.
Sally-Ann LynchNational Centre for Medical Genetics, Our Lady's Children's Hospital, Dublin 12, Ireland.
Sanjay SisodiyaDepartment of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK.
Sarju G MehtaDepartment of Medical Genetics, Cambridge University Addenbrooke's Hospital, Cambridge, UK.
Shane A McKeeNorthern Ireland Regional Genetics Service (NIRGS), Belfast City Hospital, Belfast, UK.
Shehla MohammedDepartment of Genetics, Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Simon HoldenDepartment of Medical Genetics, Cambridge University Addenbrooke's Hospital, Cambridge, UK.
Soo-Mi ParkDepartment of Medical Genetics, Cambridge University Addenbrooke's Hospital, Cambridge, UK.
Susan E HolderNorth West Thames Regional Genetics Service, Kennedy-Galton Centre, North West London Hospitals NHS Trust, Harrow, UK.
Victoria HarrisonWessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
Vivienne McConnellNorthern Ireland Regional Genetics Service (NIRGS), Belfast City Hospital, Belfast, UK.
Wayne K LamSouth East of Scotland Clinical Genetic Service, Molecular Medicine Centre, Western General Hospital, Edinburgh, UK.
Andrew J GreenNational Centre for Medical Genetics, Our Lady's Children's Hospital, Dublin 12, Ireland School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland.
Dian DonnaiFaculty of Medical and Human Sciences, Manchester Centre for Genomic Medicine, Institute of Human Development, University of Manchester, Manchester Academic Health Science Centre (MAHSC), Manchester, UK.
Maria Bitner-GlindziczClinical Genetics Department, Great Ormond Street Hospital, London, UK Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, UK.
Deirdre E DonnellyNorthern Ireland Regional Genetics Service (NIRGS), Belfast City Hospital, Belfast, UK.
Christoffer NellåkerMedical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Martin S TaylorMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
David R FitzPatrickMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Institute of Genetics and Cancer · GBGreat Ormond Street Hospital · GBGuy's Hospital · GBUniversity of Ulster · GBManchester Academic Health Science Centre · GBSt George's, University of London · GBUniversity of Cambridge · GBBirmingham Women's Hospital · GBLondon North West Healthcare NHS Trust · GBSheffield Children's NHS Foundation Trust · GBAmsterdam UMC Location University of Amsterdam · NLIstanbul University · TRNewcastle upon Tyne Hospital · GBPrincess Anne Hospital · GBUniversity of Oxford · GBWestern General Hospital · GBChurchill Hospital · GBIsfahan University of Medical Sciences · IRJohn Radcliffe Hospital · GBKingston Hospital NHS Trust · GB
Funding
Medical Research Council MC_EX_G0802457Medical Research Council MC_PC_U127561093Medical Research Council MC_PC_U127597124Wellcome Trust
Abstract
backgroundCornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS.
methodsWe screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing.
resultsPathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3] (28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1 [0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11 demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of undetected mosaic cases we used recursive partitioning to identify discriminating features in the NIPBL-positive subgroup. Filtering of the mutation-negative group on these features classified at least 18% as 'NIPBL-like'. A computer composition of the average face of this NIPBL-like subgroup was also more typical in appearance than that of all others in the mutation-negative group supporting the existence of undetected mosaic cases.
conclusionsFuture diagnostic testing in 'mutation-negative' CdLS thus merits deeper sequencing of multiple DNA samples derived from different tissues.
Indexed as
Genetic HeterogeneityMosaicismDe Lange SyndromeFaceGenetic Association StudiesHumansMutationPhenotypeClinical geneticsCopy-numberMolecular genetics
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