Institute of Human Genetics, International Centre for Life, Newcastle University, Central Parkway, Newcastle upon Tyne, UK.
European journal of human genetics: EJHG (Impact Factor: 4.35). 04/2009; 17(4):406-16. DOI: 10.1038/ejhg.2008.238
Source: PubMed


Nephronophthisis (NPHP) is an autosomal recessive kidney disorder characterized by chronic tubulointerstitial nephritis and leading to end-stage renal failure. NPHP as a renal entity is often part of a multisystem disorder and has been associated with many syndromes including Joubert syndrome (and related disorders) and Senior-Loken syndrome. Recent molecular genetic advances have allowed identification of several genes underlying NPHP. Most of these genes express their protein products, named nephrocystins, in primary cilial/basal body structures. Some nephrocystins are part of adherens junction and focal adhesion kinase protein complexes. This shared localization suggests that common pathogenic mechanisms within the kidney underlie this disease. Functional studies implicate nephrocystins in planar cell polarity pathways, which may be crucial for renal development and maintenance of tubular architecture.

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Available from: John Sayer, Oct 09, 2015
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    • "A detailed family history must be taken both to facilitate diagnosis and to highlight other individuals who should be invited for review. Appropriate investigations include renal and liver function tests; urine concentration ability, renal and hepatic ultrasound, cerebral imaging if clinically indicated, and referral to an ophthalmologist (Figure 1) [16]. After genetic counselling, blood may be sent for genetic testing (Table 2) to genetic testing organisations (e.g., or "
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    ABSTRACT: Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and a leading genetic cause of established renal failure (ERF) in children and young adults. Early presenting symptoms in children with NPHP include polyuria, nocturia, or secondary enuresis, pointing to a urinary concentrating defect. Renal ultrasound typically shows normal kidney size with increased echogenicity and corticomedullary cysts. Importantly, NPHP is associated with extra renal manifestations in 10-15% of patients. The most frequent extrarenal association is retinal degeneration, leading to blindness. Increasingly, molecular genetic testing is being utilised to diagnose NPHP and avoid the need for a renal biopsy. In this paper, we discuss the latest understanding in the molecular and cellular pathogenesis of NPHP. We suggest an appropriate clinical management plan and screening programme for individuals with NPHP and their families.
    05/2011; 2011:527137. DOI:10.4061/2011/527137
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    • "NPHP (OMIM 256100) is an autosomal recessive cystic renal disease (reviewed in [93,94]). Individuals with this disease can also suffer from situs inversus, pancreatic and hepatic fibrosis, retinal degeneration (in Senior-Løken syndrome (SLSN) and Joubert syndrome (JBTS)), complex brainstem malformation and mental retardation (JBTS). "
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    ABSTRACT: Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. They consist of a basal body, composed of two centrioles, and a protruding body, named the axoneme. Although the basic structure of all cilia is the same, numerous differences emerge in different cell types, suggesting diverse functions. In recent years many studies have elucidated the function of 9+0 primary cilia. The primary cilium acts as an antenna for the cell, and several important pathways such as Hedgehog, Wnt and planar cell polarity (PCP) are transduced through it. Many studies on animal models have revealed that during embryogenesis the primary cilium has an essential role in defining the correct patterning of the body. Cilia are composed of hundreds of proteins and the impairment or dysfunction of one protein alone can cause complete loss of cilia or the formation of abnormal cilia. Mutations in ciliary proteins cause ciliopathies which can affect many organs at different levels of severity and are characterized by a wide spectrum of phenotypes. Ciliary proteins can be mutated in more than one ciliopathy, suggesting an interaction between proteins. To date, little is known about the role of primary cilia in adult life and it is tempting to speculate about their role in the maintenance of adult organs. The state of the art in primary cilia studies reveals a very intricate role. Analysis of cilia-related pathways and of the different clinical phenotypes of ciliopathies helps to shed light on the function of these sophisticated organelles. The aim of this review is to evaluate the recent advances in cilia function and the molecular mechanisms at the basis of their activity.
    PathoGenetics 06/2009; 2(1):3. DOI:10.1186/1755-8417-2-3
  • Pediatric Nephrology 05/2010; 25(10):2193-4. DOI:10.1007/s00467-010-1539-5 · 2.86 Impact Factor
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