Nephronophthisis

Simms, Roslyn; Eley, Lorraine; Sayer, John A.

doi:10.1038/ejhg.2008.238

Cited by 59 publications

(52 citation statements)

References 77 publications

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“…This localisation prompts the question whether mutations in ANKH give rise to a ciliopathy. Although there does not seem to be a cystic kidney phenotype (common to many ciliopathies [29]), the bone abnormalities and skeletal phenotypes seen in patients with craniometaphyseal dysplasia secondary to ANKH mutations (OMIM #123000) may be consistent with an additional chemosensory/mechanosensory defect in chondrocytes. Skeletal abnormalities, which may include limb patterning defects, defects in endochondral bone, teeth and craniofacial bones are a feature of several ciliopathy syndromes [30].…”

Section: Discussionmentioning

confidence: 96%

The Pyrophosphate Transporter ANKH is Expressed in Kidney and Bone Cells and Colocalises to the Primary Cilium/Basal Body Complex

Carr

Moochhala²,

Eley³

et al. 2009

Cell Physiol Biochem

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Background/Aims: ANKH encodes a putative pyrophosphate transporter named ANKH, which regulates tissue calcification. ANKH is a transmembrane protein with at least 8 predicted transmembrane domains. Sequence analysis reveals a possible cilial localisation motif immediately after the last transmembrane segment. Here we aim to determine the subcellular localisation of ANKH in ciliated epithelial cells and murine tissue and identify colocalisation using ciliary/basal body markers. Methods: Using murine kidney, renal epithelial cells and osteoblast cells we investigated the expression and localisation of ANKH using RT-PCR, Western blotting and immunocytochemistry. Results: Here we confirm endogenous expression of ANKH mRNA and protein in whole mouse kidney as well as mouse renal epithelial cell lines M1 and mpkCCDcl4 and the osteoblast cell line MC3T3-E1. Using antibodies directed towards ANKH, we confirm cilial and basal body localisation in renal tissues and renal epithelial cells, in addition to a centrosomal localisation in dividing mpkCCDcl4 cells. We also establish that the osteoblast cell line MC3T3-E1 forms an epithelioid cell layer, with junctional complex formation and primary cilia expression. ANKH is also seen within cilial and basal body structures of MC3T3-E1 cells. An ANKH-3XFLAG construct expressed in mpkCCDcl4 cells also localises to the primary cilium/basal body complex confirming this localisation. Conclusion: We conclude that the transmembrane protein ANKH is expressed in cilia and basal body structures, and postulate a sensory role at this location.

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Section: Discussionmentioning

confidence: 96%

The Pyrophosphate Transporter ANKH is Expressed in Kidney and Bone Cells and Colocalises to the Primary Cilium/Basal Body Complex

Carr

Moochhala²,

Eley³

et al. 2009

Cell Physiol Biochem

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“…Key histology findings are tubulointerstitial fibrosis, tubular atrophy, tubular dilatation, and cyst formation. Renal ultrasound (US) reveals increased cortical echogenicity, loss of corticomedullary differentiation, and corticomedullary cysts [Salomon et al, 2009;Simms et al, 2009]. In 10-15% of cases, juvenile NPHP is accompanied by retinal involvement, which is called SLS (MIM] 266900).…”

Section: Nephronophthisis (Nphp) and Senior-loken Syndrome (Sls)mentioning

confidence: 99%

CEP290, a gene with many faces: mutation overview and presentation of CEP290base

et al. 2010

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Ciliopathies are an emerging group of disorders, caused by mutations in ciliary genes. One of the most intriguing disease genes associated with ciliopathies is CEP290, in which mutations cause a wide variety of distinct phenotypes, ranging from isolated blindness over SeniorLoken syndrome (SLS), nephronophthisis (NPHP), Joubert syndrome (related disorders) (JS[RD]), Bardet-Biedl syndrome (BBS), to the lethal Meckel-Grüber syndrome (MKS). Despite the identification of over 100 unique CEP290 mutations, no clear genotype-phenotype correlations could yet be established, and consequently the predictive power of a CEP290-related genotype remains limited. One of the challenges is a better understanding of second-site modifiers. In this respect, there is a growing interest in the potential modifying effects of variations in genes encoding other members of the ciliary proteome that interact with CEP290. Here, we provide an overview of all CEP290 mutations identified so far, with their associated phenotypes. To this end, we developed CEP290base, a locusspecific mutation database that links mutations with patients and their phenotypes (medgen.ugent.be/cep290base).

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“…The inspiration for the term nephronophthisis (ancient Greek for kidney/nephron decline) came from the observation that in contrast to more frequent cystic kidney disease such as autosomal dominant polycystic kidney disease, the kidney size in NPHP patients is often small [2]. Three clinical forms of NPHP have been distinguished by onset of end-stage kidney disease (ESKD): infantile, juvenile and adolescent NPHP which manifests with ESKD at the median ages of 1, 13 and 19 years old, respectively [3][4][5]. Initial symptoms are relatively mild and consist of polyuria, polydipsia with regular fluid intake at nighttime, secondary enuresis and anemia.…”

Section: Discussionmentioning

confidence: 99%