Autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD) are genetically distinct, with ADPKD usually caused by the genes <i>PKD1</i> or <i>PKD2</i> (encoding polycystin-1 and polycystin-2, respectively) and ARPKD caused by <i>PKHD1</i> (encoding fibrocystin/polyductin [FPC]).
To determine whether defects in other human cystoproteins have similar effects, we studied extracellular acidification and glucose metabolism in human embryonic kidney (HEK-293) cell lines with polycystic kidney and hepatic disease 1 ( PKHD1) and polycystic kidney disease (PKD) 2 ( PKD2) truncating defects along multiple sites of truncating mutations found in patients with autosomal recessive and dominant PKDs.
Autosomal dominant polycystic kidney disease (ADPKD) is typically a late-onset disease caused by mutations in PKD1 or PKD2, but about 2% of patients with ADPKD show an early and severe phenotype that can be clinically indistinguishable from autosomal recessive polycystic kidney disease (ARPKD).
Cilia were approximately 20% shorter in ARPKD than HFCT cells, but no difference in ciliary localization or total cellular expression of polycystin-2, a mechanosenory Gd(3+)-sensitive cation channel, was detected between ARPKD and HFCT cells.
Recent developments have helped elucidate the function of the autosomal dominant polycystic kidney disease proteins, polycystin-1 and polycystin-2, and have revealed the primary defect in autosomal recessive polycystic kidney disease, by positional cloning of the gene, PKHD1.
Renal tubules are predisposed to cystogenesis when a germ line mutation is inherited in either the human PKD1 or PKD2 genes in autosomal dominant polycystic kidney disease (ADPKD) or when a homozygous mutation in Tg737 is inherited in the orpk mouse model of autosomal recessive polycystic kidney disease (ARPKD).
Linkage analysis in 19 families with autosomal recessive polycystic kidney disease (ARPKD) has shown that ARPKD is not linked to the recently assigned second gene locus for autosomal dominant polycystic kidney disease (ADPKD) on chromosome 4q (PKD2).