The role of novel COQ8B mutations in glomerulopathy and related kidney defects

Asmaa S. AbuMaziad, Tarjani M. Thaker, Thomas M. Tomasiak, Chyi Chyi Chong, Maureen K. Galindo, H. Eugene Hoyme

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background and Objectives: Glomerulopathies affect kidney glomeruli and can lead to end-stage renal disease if untreated. Clinical and experimental evidence have identified numerous (>20) genetic mutations in the mitochondrial coenzyme Q8B protein (COQ8B) primarily associated with nephrotic syndrome. Yet, little else is understood about COQ8B activity in renal pathogenesis and its role in mitochondrial dysfunction. We identified additional novel COQ8B mutations in a glomerulopathy patient and aimed to define the potential structural and functional defects of COQ8B mutations. Design, Setting, Participants, and Measurements: Whole exome sequencing was performed on a Hispanic female presenting with proteinuria. Novel mutations in the COQ8B gene were identified. The effects of mutation on protein function, mitochondrial morphology, and disease progression were investigated by histopathology, transmission electron microscopy, homology modeling, and in silico structural analysis. Results: We have characterized the pathophysiology of novel COQ8B mutations, compound heterozygous for two alterations c.1037T>G (p.I346S), and c.1560G>A (p.W520X), in the progression of proteinuria in a Hispanic female. Histopathology revealed defects in podocyte structure and mitochondrial morphology. In silico and computation analyses highlight possible structural origins of COQ8B dysfunction in the presence of mutations. Conclusions: Novel mutations in COQ8B present promising biomarkers for the early detection and therapeutic targeting of mitochondrial glomerulopathy. Insights from structural modeling suggest roles of mutation-dependent alterations in COQ8B allosteric regulation, protein folding, or stability in renal pathogenesis.

Original languageEnglish (US)
Pages (from-to)60-67
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Issue number1
StatePublished - Jan 2021


  • ADCK4
  • COQ8B
  • FSGS
  • mitochondria
  • nephrotic syndrome
  • proteinuria

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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