Abstract:

Objective To summarize and review the clinical data of two children with mitochondrial nephropathy so as to improve it's knowledge. Methods Clinical data of two cases with mitochondrial nephropathy were summarized, including clinical manifestations, laboratory findings, renal pathological changes and family investigation. This study used next generation sequencing to screen 4 000 genes, including the 40 genes known to be associated with mitochondrial disease. Significant variants detected by next generation sequencing were confirmed by conventional Sanger sequencing and segregation analysis was performed using parental DNA samples. Results In two cases, one is a boy, the other is a girl. Age onset of the girl was 11.7 years. She presented with proteinuria, renal dysfunction, no extrarenal symptoms and focal segmental glomerulosclerosis (FSGS) in renal biopsy. Heterozygous p.E447 and p.G601A mutations in NPHS1 and homozygous p.D209H mutation in ADCK4 gene were detected and confirmed by next-generation sequencing and conventional Sanger sequencing, respectively. Family analysis showed that the girl had same genotype in NPHS1 gene with her father and sibling, and her homozygous p.D209H mutation in ADCK4 gene was from parents. The boy presented with congenital heart disease and mental retardation after birth, and nephrotic syndrome in few months later. Homozygous p.R360W mutation in COQ6 gene was identified and confirmed by next-generation sequencing and Sanger sequencing, respectively. Family analysis showed that homozygous p.R360W mutation in COQ6 gene inherited from his parents. Missense p.D209H and p.R360W mutations were damaging by prediction online PolyPhen and SIFT software. Protein multiple alignment showed site in p.D209H and p.R360W mutations both were conservative. Conclusion Two cases with renal phenotype were caused by casual mutations in ADCK4 and COQ6 gene, respectively. These two cases could be diagnosed as mitochondrial nephropathy. One case with mutation in ADCK4 gene presented with proteinuria, renal dysfunction, no extrarenal symptoms and FSGS in renal biopsy. The other with mutation in COQ6 gene had nephrotic syndrome, except congenital heart disease and mental retardation.