Evidence map›Paper›PMID 35902510›Full record

ArticleAngiogenesis2023

Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations.

Hiroki Hongo, Satoru Miyawaki, Yu Teranishi, Jun Mitsui, Hiroto Katoh, Daisuke Komura, Kinya Tsubota, Takashi Matsukawa, Masakatsu Watanabe, Masakazu Kurita and 21 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angiogenesis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.2field-weighted citation impact, top 11% of its field
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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Biological identity of orbital cavernous venous malformations.Arquivos brasileiros de oftalmologia · 2024
    Review
  10. SomaticStroke and vascular neurology · 2023
    Article
  11. Review
  12. Review
  13. 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

31 authors at 4 institutions in 1 country.

Hiroki HongoDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Satoru MiyawakiDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. smiya-nsu@m.u-tokyo.ac.jp.
Yu TeranishiDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Jun MitsuiDepartment of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiroto KatohDepartment of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Daisuke KomuraDepartment of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kinya TsubotaDepartment of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
Takashi MatsukawaDepartment of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Masakatsu WatanabeLaboratory of Pattern Formation, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
Masakazu KuritaDepartment of Plastic, Reconstructive and Aesthetic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
Jun YoshimuraDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
Shogo DofukuDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Kenta OharaDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Daiichiro IshigamiDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Atsushi OkanoDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Motoi KatoDepartment of Plastic, Reconstructive and Aesthetic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
Fumihiko HakunoDepartment of Animal Resource Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
Ayaka TakahashiDepartment of Animal Resource Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
Akiko KunitaDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiroyuki IshiuraDepartment of Neurology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Masahiro ShinDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Hirofumi NakatomiDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Toshitaka NagaoDepartment of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
Hiroshi GotoDepartment of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
Shin-Ichiro TakahashiDepartment of Animal Resource Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
Tetsuo UshikuDepartment of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Shumpei IshikawaDepartment of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Mutsumi OkazakiDepartment of Plastic, Reconstructive and Aesthetic Surgery, The University of Tokyo Hospital, Tokyo, Japan.
Shinichi MorishitaDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
Shoji TsujiDepartment of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Nobuhito SaitoDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
The University of Tokyo · JPTokyo Medical University · JPUniversity of Tokyo Hospital · JPOsaka University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Orbital cavernous venous malformation (OCVM) is a sporadic vascular anomaly of uncertain etiology characterized by abnormally dilated vascular channels. Here, we identify a somatic missense mutation, c.121G > T (p.Gly41Cys) in GJA4, which encodes a transmembrane protein that is a component of gap junctions and hemichannels in the vascular system, in OCVM tissues from 25/26 (96.2%) individuals with OCVM. GJA4 expression was detected in OCVM tissue including endothelial cells and the stroma, through immunohistochemistry. Within OCVM tissue, the mutation allele frequency was higher in endothelial cell-enriched fractions obtained using magnetic-activated cell sorting. Whole-cell voltage clamp analysis in Xenopus oocytes revealed that GJA4 c.121G > T (p.Gly41Cys) is a gain-of-function mutation that leads to the formation of a hyperactive hemichannel. Overexpression of the mutant protein in human umbilical vein endothelial cells led to a loss of cellular integrity, which was rescued by carbenoxolone, a non-specific gap junction/hemichannel inhibitor. Our data suggest that GJA4 c.121G > T (p.Gly41Cys) is a potential driver gene mutation for OCVM. We propose that hyperactive hemichannel plays a role in the development of this vascular phenotype.

Indexed as

Gain of Function MutationVascular MalformationsEndothelial CellsGap JunctionsHumansMutationVeinsConnexinEndothelial cellGap junction proteinOrbital diseaseVascular malformationsWhole-cell voltage clamp

Identifiers

PMID35902510
PMCPMC9908695
OpenAlexW4288424376

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Registered trials

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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.