Identification of a new gene locus for adolescent nephronophthisis, on chromosome 3q22 in a large Venezuelan pedigree.

Nephronophthisis, an autosomal-recessive cystic kidney disease, is the most frequent monogenic cause for renal failure in childhood. Infantile and juvenile forms of nephronophthisis are known to originate from separate gene loci. We describe here a new disease form, adolescent nephronophthisis, that is clearly distinct by clinical and genetic findings. In a large, 340-member consanguineous Venezuelan kindred, clinical symptoms and renal pathology were evaluated. Onset of terminal renal failure was compared with that in a historical sample of juvenile nephronophthisis. Onset of terminal renal failure in adolescent nephronophthisis occurred significantly later (median age 19 years, quartile borders 16.0 and 25.0 years) than in juvenile nephronophthisis (median age 13.1 years, quartile borders 11.3 and 17.3 years; Wilcoxon test P=.0069). A total-genome scan of linkage analysis was conducted and evaluated by LOD score and total-genome haplotype analyses. A gene locus for adolescent nephronophthisis was localized to a region of homozygosity by descent, on chromosome 3q22, within a critical genetic interval of 2. 4 cM between flanking markers D3S1292 and D3S1238. The maximum LOD score for D3S1273 was 5.90 (maximum recombination fraction.035). This locus is different than that identified for juvenile nephronophthisis. These findings will have implications for diagnosis and genetic counseling in hereditary chronic renal failure and provide the basis for identification of the responsible gene.

Acquired cystic kidney disease before and after renal transplantation.

To determine the prevalence of acquired cystic kidney disease (ACKD), as reported in adults receiving long-term hemodialysis treatment, we studied 48 pediatric patients (aged 17 +/- 5.1 years) with end-stage renal disease by high-resolution ultrasonography or magnetic resonance imaging or both. Forty patients (83%) had a functioning renal transplant, with a mean transplant survival time of 3.4 years (range, 0.3 to 14.8 years); four patients were treated by hemodialysis and four by peritoneal dialysis. The mean duration of end-stage renal disease was 5.7 +/- 3.8 years. Ultrasonography detected ACKD in 12 (29%) of 42 patients, solitary cysts in 14 patients (33%), and no cysts in 16 patients (38%). In contrast, ACKD was diagnosed in only 3 of 37 patients studied by magnetic resonance imaging. In 31 patients studied by both imaging techniques. ACKD was diagnosed in three patients by magnetic resonance imaging but in 11 by ultrasonography. In patients with ACKD, the duration of end-stage renal disease was significantly longer, but renal (transplant) function was not different from that in patients with solitary cysts or no cysts. One patient with a history of 12 1/2 years of hemodialysis had multiple renal tumors that were diagnosed as renal cell carcinomas after bilateral nephrectomy. These results indicate that young patients with end-stage renal disease should be monitored regularly for the presence of ACKD, preferably by ultrasonography, even after successful renal transplantation.