Nephronophthisis related to homozygous NPHP1 gene deletion as a cause of chronic renal failure in adults

Nephronophthisis (NPH) is an autosomal recessivenephropathy with chronic tubulointerstitial involve-ment, which represents the leading cause of end-stagerenal disease (ESRD) in children and adolescents.According to the age at onset of ESRD, three forms ofNPH have been described: infantile, juvenile (the mostfrequent) and adolescent.In the juvenile form, polyuro-polydipsia starts at4–6 years, and precedes progressive renal failure, withESRD occurring around 13 years of age [1]. Mainhistological findings are tubular atrophy with irregu-larly thickened tubular basement membranes appear-ing at an early stage, interstitial fibrosis and cysts atthe corticomedullary junction and in the medulla [2].The clinical and histological presentation is similar inthe adolescent form, with a later occurrence of ESRD(median age: 19 years). Extra-renal disorders may bepresent in the juvenile form of NPH and includemainly retinal impairment of variable severity. Theclinical and histological features of the infantile formdiffer sharply from the two others: ESRD occurs in thefirst 2 years of life, and patients usually present withenlarged kidneys and widespread cyst development[2,3]. To date, four genes implicated in juvenile oradolescent forms of NPH have been identified:NPHP1, NPHP3, NPHP4 and NPHP5. The mostfrequent genetic abnormality found in NPH is a largehomozygous deletion of the NPHP1 gene [4,5]. Thesefour genes encode proteins named nephrocystins,which have various subcellular localization, includingthe primary apical cilia, focal adhesion and adherensjunction, suggesting that they play a role in theintegrity and architecture of renal tubular epithelialcells [6]. NPHP3 mutations are responsible for theadolescent form of NPH. However, mutations in thefive known genes are found in only 50–60% of NPHcases, indicating that other genes remain to bediscovered [7].NPH is a very rare cause of ESRD in adults. Wereport four cases of NPH diagnosed in adulthood, inwhich molecular study revealed homozygous deletionof NPHP1 gene.