umu.sePublications
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
Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic syndrome alter COQ8B function
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Clinical Genetics Unit, Department of Women and Children's Health, IRP Città della Speranza, University of Padova, Padova, Italy.
Show others and affiliations
2018 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 39, no 3, p. 406-414Article in journal (Refereed) Published
Abstract [en]

Mutations in COQ8B cause steroid-resistant nephrotic syndrome with variable neurological involvement. In yeast, COQ8 encodes a protein required for coenzyme Q (CoQ) biosynthesis, whose precise role is not clear. Humans harbor two paralog genes: COQ8A and COQ8B (previously termed ADCK3 and ADCK4). We have found that COQ8B is a mitochondrial matrix protein peripherally associated with the inner membrane. COQ8B can complement a Delta COQ8 yeast strain when its mitochondrial targeting sequence (MTS) is replaced by a yeast MTS. This model was employed to validate COQ8B mutations, and to establish genotype-phenotype correlations. All mutations affected respiratory growth, but there was no correlation between mutation type and the severity of the phenotype. In fact, contrary to the case of COQ2, where residual CoQ biosynthesis correlates with clinical severity, patients harboring hypomorphic COQ8B alleles did not display a different phenotype compared with those with null mutations. These data also suggest that the system is redundant, and that other proteins (probably COQ8A) may partially compensate for the absence of COQ8B. Finally, a COQ8B polymorphism, present in 50% of the European population (NM_024876.3:c.521A > G, p.His174Arg), affects stability of the protein and could represent a risk factor for secondary CoQ deficiencies or for other complex traits.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018. Vol. 39, no 3, p. 406-414
Keywords [en]
coenzyme Q deficiency, steroid-resistant nephrotic syndrome, yeast, COQ8B, mitochondrial phropathy
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-145360DOI: 10.1002/humu.23376ISI: 000424807600010PubMedID: 29194833OAI: oai:DiVA.org:umu-145360DiVA, id: diva2:1190023
Available from: 2018-03-13 Created: 2018-03-13 Last updated: 2018-06-09Bibliographically approved

Open Access in DiVA

fulltext(2133 kB)81 downloads
File information
File name FULLTEXT01.pdfFile size 2133 kBChecksum SHA-512
e27029fa1c3290217bc27a8b3b5387df528cb9748660cf9fe57069f16f5e7e6a092b8860adb9f390fe16697335e1fcd2d5d402b419fad76a5dd8f32fbafee853
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Doimo, Mara

Search in DiVA

By author/editor
Doimo, Mara
By organisation
Department of Medical Biochemistry and Biophysics
In the same journal
Human Mutation
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 81 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: 189 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