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

Journal Article · Thu Nov 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.10.102· OSTI ID:23125256

Yang, Jing ^[1]; Yang, Yuan ^[2]; Hu, Zhangxue ^[1]

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1. Department of Nephrology, West China Hospital, Sichuan University, 37 Guoxue Ally, Wuhou District, Chengdu City, Sichuan province (China)
2. Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37 Guoxue Ally, Wuhou District, Chengdu City, Sichuan province (China)

Highlights: • ADCK4 is located on human chromosome 19q13.2 and encodes the ADCK4 protein, which interacts with members of the CoQ10 biosynthesis pathway. • Mutations in the ADCK4 gene can cause CoQ10 deficiency and mitochondrial nephropathy (ADCK4-associated glomerulopathy, ADCK4-GN). • ADCK4-GN mainly manifests as steroid resistant nephrotic syndrome clinically and focal segmental glomerulosclerosis pathologically. • The C-terminal portion in ADCK4 is important and indispensable. The upstream nonsense/frameshift mutations should be considered deleterious. • CoQ10 treatment may reduce proteinuria and postpone ADCK4-GN progression. 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. CoQ{sub 10} treatment may reduce proteinuria and postpone ADCK4-GN progression.

• OSTI ID: 23125256
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 506; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
BIOPSY
BIOSYNTHESIS
HUMAN CHROMOSOMES
KIDNEYS
MITOCHONDRIA
STEROIDS