Disease relevance of NPHP3

• Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis [1].
• KIAA0678 was considered a good functional candidate gene for NPH3 and SLS3, because molecular cha- perones are involved in the etiology of renal and retinal diseases [2].

High impact information on NPHP3

• We describe mutations in NPHP3 in families with isolated NPHP and in families with NPHP with associated hepatic fibrosis or tapeto-retinal degeneration [1].
• Interventional studies in the pcy mouse have shown beneficial effects by modification of protein intake and administration of methylprednisolone, suggesting therapeutic strategies for treating individuals with NPHP3 [1].
• Three loci are associated with the juvenile, infantile and adolescent forms, on chromosomes 2q13 (NPHP1; refs 5,6), 9q22 (NPHP2; ref. 7) and 3q21 (NPHP3; ref. 8), respectively [3].
• By fluorescence in situ hybridization the chromosomal assignment of NPHP3 to chromosome 3q21-q22 was refined [4].
• In the current study, the NPHP3 genetic region was cloned and seven genes, eight expressed sequence-tagged sites, and seven microsatellites were physically localized within the critical disease interval [4].

Biological context of NPHP3

• We carried out haplotype analysis of families affected with nephronophthisis that were not linked to the NPHP1, NPHP2 or NPHP3 loci, using markers covering this region [3].
• By human-mouse synteny analysis based on expressed genes, synteny between the human NPHP3 locus on chromosome 3q and the pcy locus on mouse chromosome 9 was clearly demonstrated, thus providing the first evidence of synteny between a human and a spontaneous murine renal cystic disease [4].
• CONCLUSION: Four NPH-families were neither linked to NPHP1 nor to NPHP3, indicating further genetic heterogeneity within the group of nephronophthisis [5].

Other interactions of NPHP3

• Here we report the identification of NPHP3, encoding a novel 1,330-amino acid protein that interacts with nephrocystin [1].
• Affected individuals of two NPH3 families and one SLS family with haplotypes indicative for homozygosity by descent for the NPHP3/SLSN3 locus were studied [2].

References