Mutational analysis of the two who survived beyond post-delivery demonstrated compound heterozygous novel frameshift mutations in the nephronophthisis type 3 gene (NPHP3).
We recently reported hypomorphic NPHP3 mutations in children and young adults with isolated nephronophthisis and associated hepatic fibrosis or tapetoretinal degeneration.
We describe mutations in NPHP3 in families with isolated NPHP and in families with NPHP with associated hepatic fibrosis or tapeto-retinal degeneration.
Autosomal-dominant medullary cystic kidney disease (ADMCKD), a hereditary chronic interstitial nephropathy, recently attracted attention because of the cloning or mapping of certain gene loci, namely NPHP1, NPHP2 and NPHP3 for familial juvenile nephronophthisis (NPH) and MCKD1 and MCKD2 for the adult form of medullary cystic kidney disease.
There is extensive gene locus heterogeneity with at least three different loci for nephronophthisis (NPHP1, NPHP2, and NPHP3) and two different loci for MCKD (MCKD1 and MCKD2).
In a large Venezuelan kindred, a new type of nephronophthisis was recently identified: Adolescent nephronophthisis (NPH3) is a late-onset recessive renal cystic disorder of the nephronophthisis/medullary cystic group of diseases causing end-stage renal disease at a median age of 19 yr. With the use of a homozygosity mapping strategy, the gene (NPHP3) was previously localized to chromosome 3q22 within a critical interval of 2.4 cM.