Autosomal dominant polycystic kidney disease
(ADPKD) is a late-onset disease caused by mutations in the PKD1 or PKD2 gene.
However, a minority of patients with ADPKD show an early, severe phenotype that
is clinically overlapping with autosomal recessive polycystic kidney disease
(ARPKD). Bergmann C et al 2011 (PMID 22034641) recently described severely
affected patients with polycystic kidney disease (PKD) who carried, in addition
to their expected familial germ-line defect, additional mutations in PKD genes.
Losekoot M et al 2012 (PMID 22114106) reported for the first time about a
patient with neonatal onset of polycystic kidneys who was homozygous for an incompletely
penetrant PKD2 missense variant. Very interesting, in this patient, homozygosity
was due to uniparental disomy. Vujic M et al 2010 (PMID 20558538) reported coinheritance
of a hypomorphic PKD1 allele in trans
with an inactivating PKD1 allele as a mechanism that can cause early onset
ADPKD. The patients described by Vujic M et al 2010 were basically a phenocopy
of ARPKD. Of note, the authors highlighted how linkage studies without positive
PKHD1 mutation data may be misleading (as PKD1/PKD2 mutations and not PKHD1
mutations may be the cause of the disease). Interestingly, from the functional point
of view, Garcia-Gonzalez MA et al 2010 (PMID: 20862291) found out that placental
abnormalities contribute to the fetal demise of Pkd(-/-) embryos in murine
models (mice that are homozygous for inactivating mutations of either Pkd1 or
Pkd2 typically die in midgestation, but cystic kidney disease is unlikely to be
the cause of fetal loss, as renal function is not required to complete
gestation). As an important note regarding the genetics of polycystic kidney, it should be mentioned that multicystic kidneys is mainly a spoardic disease (read here).
