Evidence map›Paper›PMID 39257002›Full record

ArticleHGG advances2024

Familial severe skeletal Class II malocclusion with gingival hyperplasia caused by a complex structural rearrangement at the KCNJ2-KCNJ16 locus.

Reza Maroofian, Alistair T Pagnamenta, Alireza Navabazam, Ron Schwessinger, Hannah E Roberts, Maria Lopopolo, Mohammadreza Dehghani, Mohammad Yahya Vahidi Mehrjardi, Alireza Haerian, Mojtaba Soltanianzadeh and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in HGG advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

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

23 authors.

Reza MaroofianDepartment of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
Alistair T PagnamentaNational Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Alireza NavabazamFaculty of Dentistry, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Ron SchwessingerCentre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Hannah E RobertsWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Maria LopopoloWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Mohammadreza DehghaniAbortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Mohammad Yahya Vahidi MehrjardiDiabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Alireza HaerianFaculty of Dentistry, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Mojtaba SoltanianzadehFaculty of Dentistry, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Mohammad Hadi Noori KooshkiFaculty of Dentistry, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Samantha J L KnightNational Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Kerry A MillerClinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Simon J McGowanComputational Biology Research Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Nicolas ChatronService de Génétique, Hospices Civils de Lyon, Lyon, France.
Andrew T TimberlakeHansjörg Wyss Department of Plastic Surgery, NYU Langone Medical Center, New York, NY, USA.
Uirá Souto MeloMax Planck Institute for Molecular Genetics, Berlin, Germany.
Stefan MundlosMax Planck Institute for Molecular Genetics, Berlin, Germany.
David BuckWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Stephen R F TwiggClinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Jenny C TaylorNational Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Andrew O M WilkieClinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Eduardo CalpenaClinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK; Grupo de Investigación en Biomedicina Molecular, Celular y Genómica, Unidad CIBERER, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain. Electronic address: eduardo.calpenacorpas@ndcls.ox.ac.uk.

Funding

Medical Research Council MR/T031670/1Wellcome Trust 102731/Z/13/Z
6 · The paper itself

Abstract

The aim of this work was to identify the underlying genetic cause in a four-generation family segregating an unusual phenotype comprising a severe form of skeletal Class II malocclusion with gingival hyperplasia. SNP array identified a copy number gain on chromosome 1 (chr1); however, this chromosomal region did not segregate correctly in the extended family. Exome sequencing also failed to identify a candidate causative variant but highlighted co-segregating genetic markers on chr17 and chr19. Short- and long-read genome sequencing allowed us to pinpoint and characterize at nucleotide-level resolution a chromothripsis-like complex rearrangement (CR) inserted into the chr17 co-segregating region at the KCNJ2-SOX9 locus. The CR involved the gain of five different regions from chr1 that are shuffled, chained, and inserted as a single block (∼828 kb) at chr17q24.3. The inserted sequences contain craniofacial enhancers that are predicted to interact with KCNJ2/KCNJ16 through neo-topologically associating domain (TAD) formation to induce ectopic activation. Our findings suggest that the CR inserted at chr17q24.3 is the cause of the severe skeletal Class II malocclusion with gingival hyperplasia in this family and expands the panoply of phenotypes linked to variation at the KCNJ2-SOX9 locus. In addition, we highlight a previously overlooked potential role for misregulation of the KCNJ2/KCNJ16 genes in the pathomechanism of gingival hyperplasia associated with deletions and other rearrangements of the 17q24.2-q24.3 region (MIM 135400).

Indexed as

Gingival HyperplasiaMalocclusion, Angle Class IIPedigreePotassium Channels, Inwardly RectifyingFemaleGenetic LociHumansMalePhenotypePolymorphism, Single NucleotideSOX9 Transcription FactorKCNJ2 protein, humanPotassium Channels, Inwardly RectifyingSOX9 Transcription Factorchromoanagenesischromothripsisenhancer hijackinggingival hyperplasiaKCNJ16KCNJ2malocclusionmandibular retrognathismmaxillary prognathismmaxillary protrusionneo-TAD

Identifiers

PMID39257002
PMCPMC11465088

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.