Nephronophthisis (NPHP)
As the name suggests, Nephronophthisis (NPHP, from Greek νεΦÏóς [nephros] meaning “kidneyâ€) is a genetic disorder that affects the kidneys of children. NPHP is considered a rare genetic disorder with an incidence estimated at less than 1:100,000 live births. Although rare, Nephronophthisis is the most frequent genetic cause of kidney failure during the first three decades of life.
NPHP is a heterogenetic autosomal recessive disorder, characterized by renal cysts at the corticomedullary border and variable extrarenal manifestation, including retinitis pigmentosa, liver fibrosis, cerebellar vermis aplasia, and situs inversus.
Mutations of six genes (NPHP1-NPHP6) have been identified to cause nephronophthisis. The NPHP gene products (nephrocystins) are quite dissimilar, but share a unique subcellular localization, the cilium/basal body/centrosome complex, where they interact with each other and focal adhesion molecules, PACS-1 (secretory pathway), retinitis pigmentosa GTPase regulator (RPGR), calmodulin and ATF4 (a transcription factor implicated in cAMPdependent renal cyst formation), indicating a broad spectrum of functional roles.
Morphology of nephronophthisis (NPHP). Top, left: Macroscopic pathology reveals cysts that arise from the corticomedullary junction of normal-sized kidneys. Top, right: Renal ultrasound demonstrates increased echogenicity, loss of corticomedullary differentiation, and the presence of cysts. In contrast to polycystic kidney disease (PKD), in NPHP, cysts are concentrated at the corticomedullary border and kidneys are not enlarged. Bottom: Renal histology in NPHP shows the characteristic triad of renal tubular (and glomerular) cysts, tubular membrane disruption, and tubulointerstitial cell infiltrates with interstitial fibrosis and periglomerular fibrosis.
[Taken from Hildebrandt F, Zhou W (2007). Nephronophthisis-Associated Ciliopathies. J Am Soc Nephrol 18: 1855-1871].
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