Abstract
Nephronophthisis (NPHP) is an autosomal recessive tubulointerstitial nephropathy and it is also one of the most frequent genetic disorders causing end stage renal disease in children.
We experienced the case of an 8-year-old female who demonstrated NPHP due to a homozygous deletion of NPHP1. She had renal dysfunction, but no abnormalities as detected by a school urine test. Her development was normal. She had polyuria (2401ml/day), and a renal concentration defect (specific gravity 1.003), but no proteinuria or hematuria was observed. She had renal dysfunction (BUN 32.2mg/dl, Cr 1.36mg/dl, cystatinC 1.82mg/l, 24hr creatinine clearance 38.7ml/min/1.73m2, β2microgloblin 0.58 mg/ml).
She was near-sighted, and during an ophthalmological examination, a color irregularity was seen in the ocular fundus, and subnormal electro-retinogram findings were also revealed. Small cysts were observed on kidney MRI. In a kidney biopsy, glomerulosclerosis and chronic tubulointerstitial nephritis were observed. We diagnosed the patient to have NPHP, and performed a polymerase chain reaction analysis of NPHP1, and a large deletion of NPHP1 was thus confirmed. A high density single nucleotide polymorphism (SNP) array was able to identify deletions in both alleles of the 2q13 region, including a part of MALL and all of NPHP1. Therefore, NPHP was considered to have been affected by the homozygous deletion of NPHP1. In addition, the patient had ocular manifestations, and was thus diagnosed to have Senior-Loken syndrome. Many patients with such a NPHP1 gene mutation also have a deletion of the MALL gene. The relationship between the MALL gene and the pathology of NPHP is still unclear. Recently, both NPHP1 and MALL genes are being studied in association with eye manifestation. The SNP array is thus considered to be a good method for performing a detailed analysis of NPHP1.
