A novel SCNN1G mutation in a PHA I infant patient correlates with nephropathy
Autor: | Ru-Yuan Zhu, Liping Yin, Huan Zhu, Li Huang |
---|---|
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Epithelial sodium channel Programmed cell death Pseudohypoaldosteronism Mutant Biophysics Apoptosis medicine.disease_cause Biochemistry Nephropathy 03 medical and health sciences 0302 clinical medicine medicine Animals Humans PTEN Epithelial Sodium Channels Molecular Biology Exome sequencing Mutation biology Chemistry Infant Cell Biology medicine.disease Rats 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Cancer research Kidney Diseases |
Zdroj: | Biochemical and Biophysical Research Communications. 519:415-421 |
ISSN: | 0006-291X |
Popis: | Systematic form of pseudohypoaldosteronism Type I (PHA I) is a rare recessive homozygous inherited syndrome characterized by severe salt loss, hyperkalemia, hyponatremia, metabolic acidosis, hyperaldosteronism and hyperreninemia. It is caused by mutations in one of the genes encoding the α, β and γ subunits of epithelial sodium channels (ENaC). In this study, we performed whole exome sequencing on an infant patient with PHA I as well as nephropathy. The result presented a novel homozygous six-base deletion in the γ subunit encoding gene SCNN1G. Then we correlated the mutant to kidney damage, along with transcriptional alterations of genes involved in inflammation, oxidative stress and apoptosis, via in vitro and in vivo tests. In addition, it was demonstrated that the SCNN1G defects triggered programmed cell death via inhibiting miR-21 and upregulating PTEN, which then orchestrated the key downstream regulators, including Bcl2, Bax2, and cleaved Caspse-3 in a way that favors cell apoptosis. The study enhances our understanding of the pathophysiology of the disorder of PHA I and the mechanisms of renal damage induced by the novel defect. |
Databáze: | OpenAIRE |
Externí odkaz: |