These approaches allowed to establish genetic diagnoses in 24% of the patients screened, widened the spectrum of genetic disease entities presenting with SRNS phenotype (<i>COL4A3-5, CLCN5</i>), and contributed to the discovery of new disease causing genes (<i>MYOE1, PTPRO</i>).
Because we could detect variants in COQ6 and could start treatment by coenzyme Q10 (CoQ10) in his very early stage of SRNS, the patient achieved complete remission.
We recently reported that individuals with mutations in COQ6, a coenzyme Q (also called CoQ<sub>10</sub>, CoQ, or ubiquinone) biosynthesis pathway enzyme, develop SRNS with sensorineural deafness, and demonstrated the beneficial effect of CoQ for maintenace of kidney function.
Patients with ADCK4 mutations had lower coenzyme Q10 levels, and coenzyme Q10 supplementation ameliorated renal disease in a patient with this particular mutation, suggesting a potential therapy for patients with steroid-resistant nephrotic syndrome with ADCK4 mutations.
The most common mutated genes were ADCK4 (6.67%), NPHS1 (5.83%), WT1 (5.83%), and NPHS2 (3.33%), and the difference in the frequencies of ADCK4 and NPHS2 mutations between this study and a study on monogenic causes of SRNS in the largest international cohort of 1,783 different families was significant.
Mutations in eight of them (PDSS1, PDSS2, COQ2, COQ4, COQ6, ADCK3, ADCK4, and COQ9) cause primary CoQ(10) deficiency, a heterogeneous group of disorders with variable age of onset (from birth to the seventh decade) and associated clinical phenotypes, ranging from a fatal multisystem disease to isolated steroid resistant nephrotic syndrome (SRNS) or isolated central nervous system disease.
ADCK4-related glomerulopathy is an important differential diagnosis in adolescents with steroid-resistant nephrotic syndrome (SRNS) and/or chronic kidney disease (CKD) of unknown origin.
Mutations in eight of them (PDSS1, PDSS2, COQ2, COQ4, COQ6, ADCK3, ADCK4, and COQ9) cause primary CoQ(10) deficiency, a heterogeneous group of disorders with variable age of onset (from birth to the seventh decade) and associated clinical phenotypes, ranging from a fatal multisystem disease to isolated steroid resistant nephrotic syndrome (SRNS) or isolated central nervous system disease.
Recessive CRB2 mutations were recently reported to cause both steroid resistant nephrotic syndrome and prenatal onset ventriculomegaly with kidney disease.
Variants affecting CRB2 function have also been identified in four families with steroid resistant nephrotic syndrome, but without any other known systemic findings.