Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Revertant mosaicism repairs skin lesions in a patient with keratitis-ichthyosis-deafness syndrome by second-site mutations in connexin 26
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.ORCID iD: 0000-0001-6085-6749
Show others and affiliations
2017 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 6, p. 1070-1077Article in journal (Refereed) Published
Abstract [en]

Revertant mosaicism(RM) is a naturally occurring phenomenon where the pathogenic effect of a germline mutation is corrected by a second somatic event. Development of healthy-looking skin due to RM has been observed in patients with various inherited skin disorders, but not in connexin-related disease. We aimed to clarify the underlying molecular mechanisms of suspected RM in the skin of a patient with keratitis-ichthyosis-deafness (KID) syndrome. The patient was diagnosed with KID syndrome due to characteristic skin lesions, hearing deficiency and keratitis. Investigation of GJB2 encoding connexin (Cx) 26 revealed heterozygosity for the recurrent de novo germline mutation, c. 148G>A, p. Asp50Asn. At age 20, the patient developed spots of healthy-looking skin that grew in size and number within widespread erythrokeratodermic lesions. Ultradeep sequencing of two healthy-looking skin biopsies identified five somatic nonsynonymous mutations, independently present in cis with the p. Asp50Asn mutation. Functional studies of Cx26 in HeLa cells revealed co-expression of Cx26-Asp50Asn and wild-type Cx26 in gap junction channel plaques. However, Cx26-Asp50Asn with the second-site mutations identified in the patient displayed no formation of gap junction channel plaques. We argue that the second-site mutations independently inhibit Cx26-Asp50Asn expression in gap junction channels, reverting the dominant negative effect of the p. Asp50Asn mutation. To our knowledge, this is the first time RM has been reported to result in the development of healthy-looking skin in a patient with KID syndrome.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS , 2017. Vol. 26, no 6, p. 1070-1077
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-324349DOI: 10.1093/hmg/ddx017ISI: 000400911000004PubMedID: 28158657OAI: oai:DiVA.org:uu-324349DiVA, id: diva2:1110243
Funder
Swedish Research Council, K2013-57X-22309-3Available from: 2017-06-15 Created: 2017-06-15 Last updated: 2017-06-15Bibliographically approved

Open Access in DiVA

fulltext(579 kB)75 downloads
File information
File name FULLTEXT01.pdfFile size 579 kBChecksum SHA-512
14c78bbe021c86de0e1793f2d41bbf3acf5b1b0df2eeebb9f151d520d56717b354b171b269d9aeef2abbccbcd911a76163d1afbeef88eb9642a8e277a5b0b43e
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Gudmundsson, SannaWilbe, MariaEkvall, SaraAmeur, AdamVirtanen, MarieVahlquist, AndersTörmä, HansBondeson, Marie-Louise
By organisation
Science for Life Laboratory, SciLifeLabDepartment of Immunology, Genetics and PathologyDermatology and Venereology
In the same journal
Human Molecular Genetics
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 75 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 498 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf