Identification of a new mutation of the NPHP1 gene


Kidney cystic diseases are inherited disorders causing chronic renal failure. According to the genetic defect they are classified as diseases of the primary ciliary complex and uromodulin-associated diseases. Mutations in genes coding for ciliary proteins are the basis of a broad category of genetic diseases, called ciliopathies. To date, three important ciliopathies are known: the autosomal dominant form and the recessive shape of the polycystic kidney and the nephronophthisis (NPHP).

Juvenile Nephronophthisis (NPHP) is a progressive renal tubulo-interstitial disorder with a form of autosomal recessive inheritance that progresses inexorably towards terminal renal failure. Three different forms have been distinguished: juvenile (NPH1), infantile (NPH2) and adolescent (NPH3). Juvenile Nephronophthisis or nephronophthisis type 1 (NPH1), is the most frequent form. In most patients with a suspected diagnosis of NPHP, based primarily on clinical and radiological data, the deletion in homozygous NPHP1 is present in 20-40% of cases. Heterozygous deletions are found in 6% of patients, with concomitant mutation of the NPHP1 gene on the second allele.

In this study we subjected to genetic screening 6 patients with suspected NPHP causing chronic renal failure, belonging to 6 families. The genetic screening identified in 2/6 patients a deletion of exons 5-7-20 and in 4/6 patients an heterozygous deletion of exon 20 and an  heterozygous deletion on exon 17 not yet described in literature.

Our results suggest that genetic screening should be included in the diagnostic procedure of patients with suspected nephronophthisis and that it may be used alternatively to  renal biopsy.

Keywords: Nephronophthisis, NPHP1 gene, Ciliopathies.

Sorry, this entry is only available in Italian.


Le malattie cistiche renali sono patologie ereditarie e rappresentano una causa importante di insufficienza renale cronica terminale (1). In base alle modalità di trasmissione, la classificazione tradizionale suddivideva le patologie cistiche renali in autosomiche dominanti, autosomiche recessive e X-linked. Oggi, l’identificazione dei geni responsabili di queste malattie e lo studio del loro prodotto proteico, hanno permesso di far luce sui meccanismi patogenetici che sono alla base della formazione delle cisti e di riclassificare le suddette malattie in relazione al difetto genetico associato in: malattie del complesso ciliare primitivo e malattie uromodulina-associate (1 , 2). 

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