Case Report: A Novel In-Frame Deletion of Leading to Nephronophthisis and Early Onset Kidney Failure

Variants in the () are a rare cause of nephronophthisis-related ciliopathies (NPHP-RC). A reduction in urinary concentration and a progressive chronic tubulointerstitial nephropathy with corticomedullary cysts are the major characteristic features of NPHP. NPHP demonstrates phenotypic and genetic heterogeneity with at least 25 different recessive genes associated with the disease. We report a female, from a consanguineous family, who presented age 9 years with echogenic kidneys with loss of cortico-medullary differentiation and progressive chronic kidney disease reaching kidney failure by 10 years of age. A novel homozygous in-frame deletion (NM_032,575.3: c.560_574delACCATGTCAACGATT, p.H188_Y192del) in was identified using whole exome sequencing (WES) that segregated from each parent. The five amino acid deletion disrupts the alpha-helix of GLIS2 zinc-finger motif with predicted misfolding of the protein leading to its predicted pathogenicity. This study broadens the variant spectrum of variants leading to NPHP-RC. WES is a suitable molecular tool for children with kidney failure suggestive of NPHP-RC and should be part of routine diagnostics in kidney failure of unknown cause, especially in consanguineous families.