Clinical and genetic diagnosis of familial juvenile nephronophthisis

Objectives Juvenile nephronophthisis is one of the most common genetic causes of chronic renal fai-lure in children. Its clinical diagnosis is difficult because of the nonspecific symptoms,so the diagnosis is mostly relied on the gene analysis. However,no genetic diagnosis has been reported in China yet. One case of genetic diagnosis of juvenile in one Chinese boy was reported. Methods The boy,9 years old,was admitted because of renal failure and anemia for 6 months. His sister died of uremia at age of 6 and had anemia at 1 year old. The boy looked pale. His haemoglobulin was 56 g/L,the urine sediment examination was normal,the specific gravity of urine was 1.005 and clearance of creatinine was 8.76 ml/(min·1.73 m2). The histological features consisted of the disintegration of tubular basement membrane,the atrophy and dilation of renal tubules,the interstitial cell infiltration and fibrosis. The peripheral blood DNA was extracted from this boy and his parents. Gene analysis was performed by PCR amplification of satellite markers which located within the known homologous deletion of NPHP1,including del-2,del-9, del-16,del-5-(5)2, del-10, and markers outside the deletion(RanBP11/12 and D2S1896)were used as controls. Results The boy was diagnosed with chronic renal failure according to his medical history and decreased Ccr. Also he was diagnosed with NPH-MCKD clinically by family history and pathological characteristics. He was suspected to have juvenile nephronophthisis based on autosomal recessive inheritance and the age of renal failure. By PCR amplification,the satellite markers of del-2,del-9,del-5-(5)2 and del-10 were missed,which indicated that there was the common large homologous deletion(250 kb)in the NPHP1. So the diagnosis of juvenile nephronophthisis was confirmed. Conclusions Nephronophthisis would be suspected by clinical manifestations and pathological findings,and the confirmation come from gene analysis. The confirmation of diagnosis could contribute to the reasonable management for such patients. It was the first juvenile nephronophthisis case confirmed by gene analysis for Chinese.