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Many genes-one disease? Genetics of nephronophthisis (NPHP) and NPHP-associated disorders

Lookup NU author(s): Dr Shalabh Srivastava, Dr Elisa MolinariORCiD, Professor John SayerORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 Srivastava, Molinari, Raman and Sayer. Nephronophthisis (NPHP) is a renal ciliopathy and an autosomal recessive cause of cystic kidney disease, renal fibrosis, and end-stage renal failure, affecting children and young adults. Molecular genetic studies have identified more than 20 genes underlying this disorder, whose protein products are all related to cilia, centrosome, or mitotic spindle function. In around 15% of cases, there are additional features of a ciliopathy syndrome, including retinal defects, liver fibrosis, skeletal abnormalities, and brain developmental disorders. Alongside, gene identification has arisen molecular mechanistic insights into the disease pathogenesis. The genetic causes of NPHP are discussed in terms of how they help us to define treatable disease pathways including the cyclic adenosine monophosphate pathway, the mTOR pathway, Hedgehog signaling pathways, and DNA damage response pathways. While the underlying pathology of the many types of NPHP remains similar, the defined disease mechanisms are diverse, and a personalized medicine approach for therapy in NPHP patients is likely to be required.

Publication metadata

Author(s): Srivastava S, Molinari E, Raman S, Sayer JA

Publication type: Review

Publication status: Published

Journal: Frontiers in Pediatrics

Year: 2018

Volume: 5

Online publication date: 05/01/2018

Acceptance date: 14/12/2017

ISSN (electronic): 2296-2360

Publisher: Frontiers Media S.A.


DOI: 10.3389/fped.2017.00287