Candidate gene analysis of KIAA0678 encoding a DnaJ-like protein for adolescent nephronophthisis and Senior-Løken syndrome type 3.

Nephronophthisis (NPH), an autosomal recessive cystic kidney disease, causes progressive renal failure. The gene for adolescent nephronophthisis (NPHP3) has been mapped to chromosome 3q21-->q22. Senior-Løken syndrome (SLS) describes the association of NPH and Leber congenital amaurosis. Recently a locus for Senior-Løken syndrome (SLSN3) has been localized on chromosome 3q21-->q22 containing the whole critical NPHP3 region. Within the critical NPHP3/SLSN3 region we identified the gene KIAA0678 encoding a DnaJ-like protein. 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. Analysis of the genomic structure of KIAA0678 identified 25 exons. For mutational analysis all exons and intron-exon boundaries were amplified and directly sequenced. Affected individuals of two NPH3 families and one SLS family with haplotypes indicative for homozygosity by descent for the NPHP3/SLSN3 locus were studied. No mutation in KIAA0678 was detected. We conclude, KIAA0678 most likely is not responsible for NPH and SLS in the patients studied.