1. Biochem Soc Trans. 2021 Jun 30;49(3):1205-1220. doi: 10.1042/BST20200791.

Molecular genetics of renal ciliopathies.

Barroso-Gil M(1), Olinger E(1), Sayer JA(1)(2)(3).

Author information:
(1)Translational and Clinical Research Institute, Faculty of Medical Sciences, 
Newcastle University, Central Parkway, Newcastle Upon Tyne NE1 3BZ, U.K.
(2)The Newcastle upon Tyne Hospitals NHS Foundation Trust, Renal Services, 
Freeman Road, Newcastle Upon Tyne NE7 7DN, U.K.
(3)NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle 
Upon Tyne NE4 5PL, U.K.

Renal ciliopathies are a heterogenous group of inherited disorders leading to an 
array of phenotypes that include cystic kidney disease and renal interstitial 
fibrosis leading to progressive chronic kidney disease and end-stage kidney 
disease. The renal tubules are lined with epithelial cells that possess primary 
cilia that project into the lumen and act as sensory and signalling organelles. 
Mutations in genes encoding ciliary proteins involved in the structure and 
function of primary cilia cause ciliopathy syndromes and affect many organ 
systems including the kidney. Recognised disease phenotypes associated with 
primary ciliopathies that have a strong renal component include autosomal 
dominant and recessive polycystic kidney disease and their various mimics, 
including atypical polycystic kidney disease and nephronophthisis. The molecular 
investigation of inherited renal ciliopathies often allows a precise diagnosis 
to be reached where renal histology and other investigations have been unhelpful 
and can help in determining kidney prognosis. With increasing molecular 
insights, it is now apparent that renal ciliopathies form a continuum of 
clinical phenotypes with disease entities that have been classically described 
as dominant or recessive at both extremes of the spectrum. Gene-dosage effects, 
hypomorphic alleles, modifier genes and digenic inheritance further contribute 
to the genetic complexity of these disorders. This review will focus on recent 
molecular genetic advances in the renal ciliopathy field with a focus on cystic 
kidney disease phenotypes and the genotypes that lead to them. We discuss recent 
novel insights into underlying disease mechanisms of renal ciliopathies that 
might be amenable to therapeutic intervention.

© 2021 The Author(s). Published by Portland Press Limited on behalf of the 
Biochemical Society.

DOI: 10.1042/BST20200791
PMID: 33960378 [Indexed for MEDLINE]