Evidence map›Paper›PMID 22466645›Full record

ArticleThe Journal of clinical investigation2012

Revertant mosaicism in a human skin fragility disorder results from slipped mispairing and mitotic recombination.

Dimitra Kiritsi, Yinghong He, Anna M G Pasmooij, Meltem Onder, Rudolf Happle, Marcel F Jonkman, Leena Bruckner-Tuderman, Cristina Has

Open access · bronzeAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

20 citing papers in PubMed, 59 citations in OpenAlex.

  1. Stairways to Advanced Therapies for Epidermolysis Bullosa.Cold Spring Harbor perspectives in biology · 2023
    Review
  2. Review
  3. Review
  4. Investigational Treatments for Epidermolysis Bullosa.American journal of clinical dermatology · 2021
    Review
  5. A novel frameshift mutation in theExperimental and therapeutic medicine · 2020
    Article
  6. A six-attribute classification of genetic mosaicism.Genetics in medicine : official journal of the American College of Medical Genetics · 2020
    Review
  7. Review
  8. Kindler syndrome: a rare case report from Greece.Oxford medical case reports · 2019
    Article
  9. Article
  10. Revertant mosaicism in genodermatoses.Cellular and molecular life sciences : CMLS · 2017
    Review
  11. Article
  12. Expanding the Mutation Spectrum of Ichthyosis with Confetti.The Journal of investigative dermatology · 2016
    Article
  13. Article
  14. Mechanisms of natural gene therapy in dystrophic epidermolysis bullosa.The Journal of investigative dermatology · 2014
    Article
  15. [How frequently does genetic mosaicism occur in the skin?].Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete · 2014
    Review
  16. [The many facets of inherited skin fragility].Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete · 2014
    Article
  17. Article
  18. Review
  19. Review
  20. Review
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

8 authors at 5 institutions in 3 countries.

Dimitra KiritsiDepartment of Dermatology, University Medical Center Freiburg, Freiburg, Germany.
Yinghong He
Anna M G Pasmooij
Meltem Onder
Rudolf Happle
Marcel F Jonkman
Leena Bruckner-Tuderman
Cristina Has
University of Freiburg · DEUniversity Medical Center Freiburg · DEDialyse Centrum Groningen · NLGazi University · TRUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spontaneous gene repair, also called revertant mosaicism, has been documented in several genetic disorders involving organs that undergo self-regeneration, including the skin. Genetic reversion may occur through different mechanisms, and in a single individual, the mutation can be repaired in various ways. Here we describe a disseminated pattern of revertant mosaicism observed in 6 patients with Kindler syndrome (KS), a genodermatosis caused by loss of kindlin-1 (encoded by FERMT1) and clinically characterized by patchy skin pigmentation and atrophy. All patients presented duplication mutations (c.456dupA and c.676dupC) in FERMT1, and slipped mispairing in direct nucleotide repeats was identified as the reversion mechanism in all investigated revertant skin spots. The sequence around the mutations demonstrated high propensity to mutations, favoring both microinsertions and microdeletions. Additionally, in some revertant patches, mitotic recombination generated areas with homozygous normal keratinocytes. Restoration of kindlin-1 expression led to clinically and structurally normal skin. Since loss of kindlin-1 severely impairs keratinocyte proliferation, we predict that revertant cells have a selective advantage that allows their clonal expansion and, consequently, the improvement of the skin condition.

Indexed as

MosaicismRecombination, GeneticAdolescentAdultBase SequenceBlisterChildConsanguinityEpidermolysis BullosaFemaleFrameshift MutationHumansINDEL MutationMaleMembrane ProteinsNeoplasm ProteinsFERMT1 protein, humanMembrane ProteinsNeoplasm Proteins

Identifiers

PMID22466645
PMCPMC3336993
OpenAlexW2041750650

What OpenQuestion holds

Textmetadata
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.