Multicystic Dysplastic Kidney and Variable Phenotype in a Family with a Novel Deletion Mutation of PAX2

Fletcher, Jeffery; Hu, Min; Berman, Yemima; Collins, Felicity; Grigg, John; McIVER, M.; Jüppner, Harald; Alexander, Stephen I.

doi:10.1681/asn.2005030239

Cited by 61 publications

(46 citation statements)

References 34 publications

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“…Vesicoureteral reflux may be an associated finding and although the majority may undergo spontaneous resolution, severe cases may be complicated by recurrent urinary tract infections and hydronephrosis necessitating surgical intervention. 3,18,22 Auditory system High frequency hearing loss presenting in childhood can be identified in up to 10% of affected individuals. 9 High frequency hearing loss is unusual in childhood.…”

Section: Renal Findingsmentioning

confidence: 99%

Renal coloboma syndrome

Schimmenti

2011

Eur J Hum Genet

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In association withRenal coloboma syndrome Renal coloboma syndrome (RCS), also called papillorenal syndrome, is an autosomal dominant condition characterized by optic nerve dysplasia and renal hypodysplasia. The eye anomalies consist of a wide and sometimes excavated dysplastic optic disc with the emergence of the retinal vessels from the periphery of the disc, frequently called optic nerve coloboma or morning glory anomaly. Associated findings may include a small corneal diameter, retinal coloboma, scleral staphyloma, optic nerve cyst and pigmentary macular dysplasia. The kidney abnormalities consist of small and abnormally formed kidneys known as renal hypodysplasia. Histologically, kidneys exhibit fewer than the normal number of glomeruli and these glomeruli are enlarged, a finding called oligomeganephronia. Consequences of the ocular malformations include decreased visual acuity and retinal detachment. Consequences of the renal hypodysplasia include hypertension, proteinuria and renal insufficiency that frequently progresses to end-stage kidney disease. High frequency hearing loss has been reported. Autosomal dominant mutations in PAX2 can be identified in nearly half of all patients with clinical findings suggestive of RCS, however, the majority of published cases have mutations in PAX2, thus biasing the known information about the phenotype.

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Section: Renal Findingsmentioning

confidence: 99%

Renal coloboma syndrome

Schimmenti

2011

Eur J Hum Genet

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“…The renal abnormalities in renal-coloboma syndrome include vesicoureteric reflux, renal hypoplasia, multicystic or dysplastic kidneys, and renal failure. 30,31 The age at presentation and rate of progression to renal failure vary even within families. Ocular features vary from optic disc pits to large chorioretinal coloboma, and abnormalities are usually asymmetrical.…”

Section: Colobomamentioning

confidence: 99%

“…33 Fewer than 20% of patients have associated sensorineural hearing loss, seizures, Arnold-Chiari malformations, or skin and joint laxity. 30 Patients with papillorenal syndrome should be monitored for ophthalmic complications and other family members screened carefully for optic disc defects. PAX2 mutations do not occur in the CHARGE or COACH syndromes and do not cause iris coloboma.…”

Section: Colobomamentioning

confidence: 99%

Retinal Abnormalities Characteristic of Inherited Renal Disease

Savige

Ratnaike

Colville

2011

Journal of the American Society of Nephrology

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“…A lterations in the PKD1 and PKD2 genes account for cases of autosomal dominant polycystic kidney disease (ADPKD) with a relative frequency of approximately 85 and 15%, respectively (1)(2)(3). PKD1 encodes polycystin-1 (PC1), a large 4302-amino acid membrane protein that participates in multiprotein complexes that are involved in cell-matrix and cell-cell interactions and signaling (4,5).…”

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confidence: 99%

Stable Knockdown of Polycystin-1 Confers Integrin-α2β1–Mediated Anoikis Resistance

Battini¹,

Fedorova²,

Macip³

et al. 2006

Journal of the American Society of Nephrology

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The mechanisms of action of polycystin-1 (PC1) have been difficult to dissect because of its interaction with multiple factors, the heterogeneity of the genetic mutations, and the complexity of the experimental animal models. Here, stable knockdown of PC1 in MDCK epithelial cells was achieved by lentiviral-mediated delivery of a specific small interfering RNA for PKD1. The reduction of PC1 expression prevented tubulogenesis in three-dimensional collagen type I culture in response to hepatocyte growth factor and induced formation of cysts. PC1 knockdown created a condition of haploinsufficiency that led to hyperproliferation, increased adhesion to collagen type I, and increased apoptosis. It was shown that the suppression of PC1 was associated with the increased expression of integrin-␣2␤1 and reduced apoptosis in cells grown on collagen type I. The engagement of integrin-␣2␤1 seemed to be essential for the survival because PC1 knockdown cells were significantly less susceptible to anoikis by a mechanism that was reversible by anti-integrin-␣2␤1 blocking antibodies. Overall, these data link integrin-␣2␤1 to some of the biologic functions that are ascribed to PC1 and establish the potential of this approach for the direct study of PC1 functions in a genetically defined background. Furthermore, these findings indicate that reduction of PC1 expression levels, rather than the loss of heterozygosity, may be sufficient to induce cystogenesis.J Am Soc Nephrol 17: 3049 -3058, 20063049 -3058, . doi: 10.1681 A lterations in the PKD1 and PKD2 genes account for cases of autosomal dominant polycystic kidney disease (ADPKD) with a relative frequency of approximately 85 and 15%, respectively (1-3). PKD1 encodes polycystin-1 (PC1), a large 4302-amino acid membrane protein that participates in multiprotein complexes that are involved in cell-matrix and cell-cell interactions and signaling (4,5). Through the heterodimerization with PC2, a nonselective cationic channel that is encoded by the PKD2 gene, PC1 can function as a gating receptor to control calcium influx (6). The interdependent functions of PC1 and PC2 in kidney are supported by the overlapping ADPKD phenotypic manifestation that is caused by mutations of either gene, although the severity and the progression of the disease are exacerbated when PKD1 is involved. The co-localization of the polycystins in primary cilia suggests their involvement in a cellular mechanosensory system (7). These findings are supported by the evidence that polycystic renal phenotypes arise from the mutation or deletion of various ciliary and adhesion proteins (8 -10). To date, however, it has been difficult to define clearly the functions of PC1 and the molecular mechanisms of cystogenesis that it controls. In part, this difficulty derives from the heterogeneity of the genetic mutations that are identified in patients with ADPKD as well as from the lack of functionally characterized mutants. Furthermore, most of the animal models for polycystic kidney share phenotypic manifestations, but some ...

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Multicystic Dysplastic Kidney and Variable Phenotype in a Family with a Novel Deletion Mutation of PAX2

Cited by 61 publications

References 34 publications

Renal coloboma syndrome

Renal coloboma syndrome

Retinal Abnormalities Characteristic of Inherited Renal Disease

Stable Knockdown of Polycystin-1 Confers Integrin-α2β1–Mediated Anoikis Resistance

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