Makale detayı · 2013
ADCK4 mutations promote steroid resistant nephrotic syndrome through CoQ10 biosynthesis disruption
- Yıl
- 2013
- DOI
- 10.1172/JCI69000
- Tür
- article
Veri kaynağı ayrımı
- YÖKSİS YÖKSİS makale kaydı
- YÖKSİS dergi adı Journal of Clinical Investigation
- Katalog eşleşmesi (ISSN) Journal of Clinical Investigation
- OpenAlex OpenAlex zenginleştirmesi (özet, atıf, konular)
Özet
OpenAlex · İngilizce
Identification of single-gene causes of steroid-resistant nephrotic syndrome (SRNS) has furthered the understanding of the pathogenesis of this disease. Here, using a combination of homozygosity mapping and whole human exome resequencing, we identified mutations in the aarF domain containing kinase 4 (ADCK4) gene in 15 individuals with SRNS from 8 unrelated families. ADCK4 was highly similar to ADCK3, which has been shown to participate in coenzyme Q10 (CoQ10) biosynthesis. Mutations in ADCK4 resulted in reduced CoQ10 levels and reduced mitochondrial respiratory enzyme activity in cells isolated from individuals with SRNS and transformed lymphoblasts. Knockdown of adck4 in zebrafish and Drosophila recapitulated nephrotic syndrome-associated phenotypes. Furthermore, ADCK4 was expressed in glomerular podocytes and partially localized to podocyte mitochondria and foot processes in rat kidneys and cultured human podocytes. In human podocytes, ADCK4 interacted with members of the CoQ10 biosynthesis pathway, including COQ6, which has been linked with SRNS and COQ7. Knockdown of ADCK4 in podocytes resulted in decreased migration, which was reversed by CoQ10 addition. Interestingly, a patient with SRNS with a homozygous ADCK4 frameshift mutation had partial remission following CoQ10 treatment. These data indicate that individuals with SRNS with mutations in ADCK4 or other genes that participate in CoQ10 biosynthesis may be treatable with CoQ10.
Konular
Atıflar
OpenAlex cited_by_count. WoS veya Scopus atıf sayısı değildir; o kaynaklar için ayrı kolon yoktur.
343 atıf
OpenAlex cited_by_count (önbellek / veritabanı)
Yerel katalogda bu makaleye atıf yapan 25 yayın (OpenAlex referans eşleşmesi; tam dünya listesi değildir).
- A Single Gene Cause in 29 5 of Cases of Steroid Resistant Nephrotic Syndrome 2015
- Development of a medication adherence scale for familial Mediterranean fever MASIF in a cohort of Turkish children 2015
- A Single Gene Cause in 29 5 of Cases of Steroid Resistant Nephrotic Syndrome 2015
- Mutations in nuclear pore genes NUP93 NUP205 and XPO5 cause steroid resistant nephrotic syndrome 2016
- Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly 2017
- ADCK4 Associated Glomerulopathy Causes Adolescence Onset FSGS 2016
- ADCK4 Associated Glomerulopathy Causes Adolescence Onset FSGS 2016
- title iADCK4/i -Associated Glomerulopathy Causes Adolescence-Onset FSGS/title 2015
- ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS 2015
- ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS 2015