Evidence map›Paper›PMID 38787418›Full record

ArticleHuman genetics2024

The detection of a strong episignature for Chung-Jansen syndrome, partially overlapping with Börjeson-Forssman-Lehmann and White-Kernohan syndromes.

Niels Vos, Sadegheh Haghshenas, Liselot van der Laan, Perle K M Russel, Kathleen Rooney, Michael A Levy, Raissa Relator, Jennifer Kerkhof, Haley McConkey, Saskia M Maas and 50 more

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Article in Human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

60 authors.

Niels Vos *Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Sadegheh Haghshenas *Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, N6A 5W9, Canada.
Liselot van der Laan *Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Perle K M RusselAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Kathleen RooneyVerspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, N6A 5W9, Canada.
Michael A LevyVerspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, N6A 5W9, Canada.
Raissa RelatorVerspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, N6A 5W9, Canada.
Jennifer KerkhofVerspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, N6A 5W9, Canada.
Haley McConkeyVerspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, N6A 5W9, Canada.
Saskia M MaasAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Lisenka E L M VissersDepartment of Human Genetics, Research Institute for Medical Innovation, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.
Bert B A de VriesDepartment of Human Genetics, Research Institute for Medical Innovation, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.
Rolph PfundtDepartment of Human Genetics, Research Institute for Medical Innovation, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.
Mariet W EltingAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Johanna M van HagenAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Nienke E VerbeekDepartment of Genetics, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
Marjolijn C J JongmansDepartment of Genetics, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
Phillis LakemanAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Lynne RumpingCenter for Medical Genetics, Antwerp University Hospital, University of Antwerp, Drie Eikenstraat 655, 2650, Edegem, Belgium.
Danielle G M BoschDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Antonio VitobelloUniversité de Bourgogne, Inserm U1231, Equipe GAD, Dijon, France.
Christel Thauvin-RobinetUniversité de Bourgogne, Inserm U1231, Equipe GAD, Dijon, France.
Laurence FaivreUniversité de Bourgogne, Inserm U1231, Equipe GAD, Dijon, France.
Sophie NambotUniversité de Bourgogne, Inserm U1231, Equipe GAD, Dijon, France.
Aurore GardeUniversité de Bourgogne, Inserm U1231, Equipe GAD, Dijon, France.
Marjolaine WillemsINserm U1183, Department of Clinical Genetics, Montpellier University, 34090 CHU Montpellier, Montpellier, France.
David GenevieveINserm U1183, Department of Clinical Genetics, Montpellier University, 34090 CHU Montpellier, Montpellier, France.
Gaël NicolasInserm U1245 and CHU Rouen, Department of Genetics and Reference Center for Developmental Disorders, Univ Rouen Normandie, 76000, Rouen, France.
Tiffany BusaDepartment of Medical Genetics, Timone Hospital, Marseille, France.
Annick ToutainGenetics Department, University Hospital, UMR 1253, iBrain, University of Tours, Inserm, Tours, France.
Marion GérardAPHP, Department of Genetics, Robert Debré Hospital, 75019, Paris, France.
Varoona BizaouiClinical Genetics and Neurodevelopmental Disorders, Centre Hospitalier de L'Estran, 50170, Pontorson, France.
Bertrand IsidorService de Génétique Médicale, CHU de Nantes, 44000, Nantes, France.
Giuseppe MerlaLaboratory of Regulatory and Functional Genomics, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
Maria AccadiaServizio di Genetica Medica, Ospedale Cardinale G. Panico, Tricase, LE, Italy.
Charles E SchwartzDepartment of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI, 49503, USA.
Katrin OunapDepartment of Clinical Genetics, Genetic and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia.
Mariëtte J V HofferDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Marjan M NezaratiGenetics Program, North York General Hospital, Toronto, ON, M2K 1E1, Canada.
Marie-José H van den BoogaardDepartment of Genetics, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
Matthew L TedderGreenwood Genetic Center, Greenwood, SC, 29646, USA.
Curtis RogersGreenwood Genetic Center, Greenwood, SC, 29646, USA.
Alfredo BruscoDepartment of Medical Sciences, University of Torino, Via Santena 19, 10126, Turin, Italy.
Giovanni B FerreroDepartment of Clinical and Biological Science, University of Torino, Turin, Italy.
Marta SpodenkiewiczService de Génétique, CRMR AnDDI-Rares, CHU Reims, Reims, France.
Richard SidlowDepartment of Medical Genetics and Metabolism, Valley Children's Hospital, Madera, CA, USA.
Alessandro MussaDepartment of Public Health and Pediatric Sciences, University of Torino, Turin, Italy.
Slavica TrajkovaDepartment of Medical Sciences, University of Torino, Via Santena 19, 10126, Turin, Italy.
Emma McCannLiverpool Center for Genomic Medicine, Liverpool Women's Hospital, Liverpool, UK.
Henry J MroczkowskiDepartment of Pediatrics, Le Bonheur Children's Hospital, Memphis, TN, USA.
Sandra JansenAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Laura Donker-KaatDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Floor A M DuijkersAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Kyra E StuurmanDepartment of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Marcel M A M MannensAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Mariëlle AldersAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Peter HennemanAmsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Susan M WhiteVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC, 3052, Australia.
Bekim Sadikovic *Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, N6A 5W9, Canada. bekim.sadikovic@lhsc.on.ca.
Mieke M van Haelst *Amsterdam UMC, Department of Human Genetics, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. m.vanhaelst@amsterdamumc.nl.

Funding

Genome Canada OGI-188
6 · The paper itself

Abstract

Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It is caused by pathogenic variants in the PHIP gene that encodes for the Pleckstrin homology domain-interacting protein, which is part of an epigenetic modifier protein complex. Therefore, we hypothesized that PHIP haploinsufficiency may impact genome-wide DNA methylation (DNAm). We assessed the DNAm profiles of affected individuals with pathogenic and likely pathogenic PHIP variants with Infinium Methylation EPIC arrays and report a specific and sensitive DNAm episignature biomarker for Chung-Jansen syndrome. In addition, we observed similarities between the methylation profile of Chung-Jansen syndrome and that of functionally related and clinically partially overlapping genetic disorders, White-Kernohan syndrome (caused by variants in DDB1 gene) and Börjeson-Forssman-Lehmann syndrome (caused by variants in PHF6 gene). Based on these observations we also proceeded to develop a common episignature biomarker for these disorders. These newly defined episignatures can be used as part of a multiclass episignature classifier for screening of affected individuals with rare disorders and interpretation of genetic variants of unknown clinical significance, and provide further insights into the common molecular pathophysiology of the clinically-related Chung-Jansen, Börjeson-Forssman-Lehmann and White-Kernohan syndromes.

Indexed as

DNA MethylationIntellectual DisabilityChildFemaleHaploinsufficiencyHumansMaleNeurodevelopmental Disorders

Identifiers

PMID38787418
PMCPMC11186873

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