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Genetics and pathogenesis of nephronophthisis

Patrick Niaudet, MD
Section Editors
Tej K Mattoo, MD, DCH, FRCP
Ronald D Perrone, MD
Deputy Editor
Melanie S Kim, MD


Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disorder that typically progresses to end-stage renal disease (ESRD). It is caused by mutations in a large number of genes that encode proteins involved in the function of primary cilia, basal bodies, and centrosomes resulting in renal disease and extrarenal manifestations, including retinal degeneration, cerebellar ataxia, and liver fibrosis.

The genetics and pathogenesis of NPHP will be reviewed here. The clinical manifestations and management of NPHP are discussed separately. (See "Clinical manifestations, diagnosis, and treatment of nephronophthisis".)


Patients with NPHP have gene mutations that encode components of the ciliary apparatus [1]. Although mutations in NPHP1 gene account for 20 percent of cases, at least 20 different genes have been associated with NPHP. All the genes encode proteins that are localized to the primary cilia, basal bodies, and centrosomes.

These gene defects result in the characteristic findings of NPHP:

Autosomal recessive inheritance

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Literature review current through: Nov 2017. | This topic last updated: Aug 23, 2017.
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