A novel ADCK4 mutation in a Chinese family with ADCK4-Associated glomerulopathy.

AarF domain-containing kinase 4 (ADCK4)-associated glomerulopathy (ADCK4-GN) is an inherited mitochondrial nephropathy caused by mutations in the ADCK4 gene. Herein, we report a case of ADCK4-GN. The patient, a 14-year-old Chinese male, presented with asymptomatic proteinuria and steroid resistance. A renal biopsy showed focal segmental glomerulosclerosis (FSGS) and dysmorphic mitochondria in podocytes. Coenzyme Q10 treatment was partially effective. No adverse events were observed. Next generation and Sanger sequencing analyses revealed compound heterozygous mutations (c.625C > G, p.D209H and c.918G > T, p.C306X). Both inherited mutations are located in the highly conserved ABC1 domain. The unreported nonsense mutation causes a loss of 197 amino acids from the C-terminal portion of ADCK4, suggesting a deleterious effect of the truncating mutation by abolishing ADCK4 function. In conclusion, we identified a novel ABC1 domain-localized pathogenic mutation responsible for ADCK4-GN, further supporting the importance of the C-terminal portion of ADCK4. Next generation sequencing facilitated the early diagnosis. CoQ10 treatment may reduce proteinuria and postpone ADCK4-GN progression.