#4688 ATP6V0A4 GENE MUTATION-ASSOCIATED NEPHROPATHY

Abstract Background and Aims The ATP6V0A4 gene is localized to chromosome 7q33∼34 encodes for vacuolar H+-ATPase (V-ATPase) α4 subunit. Decreased V-ATPase function due mutations in the genes could cause H+ excretion defect of α-intercalated cells renal collecting duct, resulting hereditary distal tubular acidosis (dRTA). However, crucially, no gain-of-function have been reported previously. This study reports a mutation occurred 32-year-old male with metabolic alkalosis, hypokalemia hearing loss, further explore potential pathogenic mechanisms this mutation. Method Clinical information was collected from proband his family members. Kidney tissue samples were morphological observation immunohistochemical staining. High-throughput sequencing analyses done parents. wild-type mutant plasmids constructed used transfect 293T cells. After 48 hours transfection, expression verified using WB activity measured by ultraviolet spectrophotometry. Results father both suffered severe hypertension loss. Blood tests showed hypokalemia, alkalosis insufficiency. Urinalysis indicated acidic urine. Laboratory on admission are shown Table 1. Renal biopsy suggested malignant hypertensive kidney injury. Whole-exome demonstrated that carried heterozygous c.1534G>T; p.V512L exon 15 gene. Sanger confirmed variant inherited father. results implied significantly higher tissues than control who diagnosed minimal change disease (Figure 1B).WB analysis transfected darker protein bands, suggesting 1D). compared 1E). Conclusion result indicates possibility might enhance normal physiological V-ATPase, likely contributes increased hydrogen ions thereby development 1F).