We report HNF1B screening in a cohort of 377 unrelated cases with various kidney phenotypes (hyperechogenic kidneys with size not more than +3 SD, multicystic kidney disease, renal agenesis, renal hypoplasia, cystic dysplasia, or hyperuricemic tubulointerstitial nephropathynot associated with UMOD mutation).
Familial juvenile hyperuricemic nephropathy (FJHN) is a rare autosomal dominant disease caused by mutations in the uromodulin gene (UMOD) and leading to gout, tubulointerstitial nephropathy and end-stage renal disease.
Identification and characterization of the MCKD and FJHN genes will help to clarify the pathogenesis and classification of hereditary tubulo-interstitial nephritides.
Autosomal-dominant medullary cystic kidney disease type 2 (MCKD2) is a tubulointerstitial nephropathy that causes renal salt wasting, hyperuricemia, gout, and end-stage renal failure in the fifth decade of life.
No CLCN5 mutations were detected.TP/Cr was lower in DC and CKiD with tubulointerstitial disease than in DD1 and CKiD with glomerular disease (p < 0.002).
The genetic study by panels of known genes associated with tubulointerstitial disease allowed us to discover autosomal dominant distal renal tubular acidosis associated with a de novo mutation in exon 14 of the SLC4A1 gene, which would have been impossible to diagnose clinically due to the advanced nature of the kidney disease when it was discovered.
These findings were highly suggestive of karyomegalic interstitial nephritis, which was further confirmed by exome sequencing of FAN1 gene showing an identified homozygous frameshift mutation due to a one-base-pair deletion in exon 12 (c.2616delA).The present case illustrates a rare but severe cause of hereditary interstitial nephritis, sometimes accompanied by subtle extrarenal manifestations.