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Zhang Luyan; Zhao Fei; Ding Guixia; Chen Ying; Zhao Sanlong; Chen Qiuxia; Sha Yugen; Che Ruochen; Huang Songming; Zheng Bixia; Zhang Aihua: Monogenic Causes Identified in 23.68% of Children with Steroid-Resistant Nephrotic Syndrome: A Single-Centre Study. Kidney Diseases DOI 10.1159/000534853
It is very clear that monogenetic diseases commonly underlie the clinical entity known as steroid-resistant nephrotic syndrome (SRNS) in both children and adults. The glomerular lesion associated with this clinical phenotype is focal and segmental glomerulosclerosis (FSGS), but other lesions, including minimal change and membranoproliferative glomerulonephritis, can occasionally be found.
Zhang and co-workers from the Children’s Hospital in Nanjing, China, carried out a descriptive study of a cohort of children with SRNS (n = 101) or FSGS and nephrotic syndrome (n = 11) using whole-exome sequencing with a panel of specific gene mutations (n = 71) known to be causative for nephrotic syndrome.
Causative genetic mutations were found in 24% of the cohort: WT1 (7/27), NPHS1 (3/27), ADCK4 (3/27), ANLN (2/27) and others (12/27), including phenocopy variants. The causative mutation discovery rate was highest in patients with congenital nephrotic syndrome and syndromic nephrotic syndrome. Interestingly, neither NPHS2 nor COLIV alpha mutations were observed, likely because of the young age of the cohort. The ADCK4 gene co-operates with co-enzyme Q10, raising the possibility of supplemental therapy with CoQ10 in such patients.
This study, and others, argues strongly for the routine performance of genetic testing of children with SRNS, and for such testing in congenital nephrotic syndrome and syndromic nephrotic syndrome even before steroid therapy is commenced.
