Nephronophthisis is an autosomal recessive cystic kidney disease characterized by onset of end-stage renal failure in the first 3 decades of life. The disorder is often associated with extrarenal manifestations, including liver fibrosis, retinal degeneration, and central nervous ... Nephronophthisis is an autosomal recessive cystic kidney disease characterized by onset of end-stage renal failure in the first 3 decades of life. The disorder is often associated with extrarenal manifestations, including liver fibrosis, retinal degeneration, and central nervous system abnormalities (summary by O'Toole et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of nephronophthisis, see NPHP1 (256100).
O'Toole et al. (2010) reported 3 sibs, born of consanguineous Finnish parents, with a renal disease reminiscent of nephronophthisis. All 3 patients developed moderate renal insufficiency (glomerular filtration rate at 30-40% of normal) between 20 and 29 years ... O'Toole et al. (2010) reported 3 sibs, born of consanguineous Finnish parents, with a renal disease reminiscent of nephronophthisis. All 3 patients developed moderate renal insufficiency (glomerular filtration rate at 30-40% of normal) between 20 and 29 years of age. Renal biopsies showed characteristic features of nephronophthisis, such as thickening, splitting, and attenuation of the tubular basement membrane, atrophic tubules, and mild interstitial fibrosis. Renal ultrasound revealed increased echogenicity in 3 and cysts in 2. All had hypertension. Extrarenal features included essential tremor in 3, high frequency sensorineural hearing loss in 2, and arachnoid cysts on brain imaging in 1. Two also had gout. Skeletal muscle mitochondrial respiratory activity was normal. O'Toole et al. (2010) also reported 2 sibs from a consanguineous Turkish family with a similar but more severe disorder involving end-stage renal disease by 8 and 9 years of age, respectively. Renal ultrasound and renal histology demonstrated nephronophthisis. In addition, both affected sibs showed a mitochondrial disorder with isolated complex I deficiency activity in muscle and had seizures, mental retardation, and hypertrophic dilated cardiomyopathy. One had chronic pancreatitis with pancreatic cysts, while the other had hepatic involvement.
By positional cloning of the NPHPL1 locus, followed by mutation analysis, O'Toole et al. (2010) identified homozygosity for a splice site mutation in the XPNPEP3 gene (613553.0001) in the Finnish family and a 4-bp deletion (613553.0002) in the ... By positional cloning of the NPHPL1 locus, followed by mutation analysis, O'Toole et al. (2010) identified homozygosity for a splice site mutation in the XPNPEP3 gene (613553.0001) in the Finnish family and a 4-bp deletion (613553.0002) in the XPNPEP3 gene in the Turkish family. The affected Finnish sibs were less severely affected, suggesting that a splice site mutation may have resulted in some residual protein product, whereas the affected Turkish sibs were more severely affected and had a truncating mutation predicting complete loss of protein function. O'Toole et al. (2010) postulated a defect in ciliary function as explanation for the phenotype.