Clinical and molecular heterogeneity of juvenile nephronophthisis in Italy: Insights from molecular screening

Gianluca Caridi, Monica Dagnino, Rosanna Gusmano, Fabrizio Ginevri, Luisa Murer, Luciana Ghio, Giorgio Piaggio, Maria Rosa Ciardi, Francesco Perfumo, Gian Marco Ghiggeri

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Autosomal recessive nephronophthisis (NPH) is a renal disorder histologically characterized by tubulointerstitial lesions that are, in some cases, associated with extrarenal manifestations such as tapeto-retinal degeneration or liver fibrosis. The disease is usually pauci-symptomatic in an early phase but invariably evolves to end-stage renal failure in childhood or early adulthood. The recent discovery of the NPHP1 gene (nephrocystin) has promoted research into putative genotype-phenotype correlations. We screened a population of 68 Italian children (10 multiplex families, 47 sporadic cases) with a clinical and histopathologic picture of NPH and found a large homozygous deletion at 2q13 involving nephrocystin in 30 cases, and heterozygous deletion associated with new point mutations at exons 15 (Tyr518Ter) and 17 (Arg585Ter) of the gene in two other cases. The remaining 36 children had no apparent molecular defects of nephrocystin. In spite of this genetic heterogeneity, the two groups, with and without detectable molecular defects of nephrocystin, showed similar renal defects and comparable cumulative survival considering the start of dialysis as an end- point. The unique difference observed was a less frequent requirement of dialysis in NPH1 patients with pure renal form. Finally, tapeto-retinal degeneration was associated with renal lesions in seven cases presenting deletion of the nephrocystin gene and in five sporadic cases without molecular defects. These data show that a molecular defect of nephrocystin is involved in approximately 50% of patients with NPH, and another 50% require further molecular characterization. Research therefore should now be aimed at characterizing a new locus. In spite of the molecular heterogeneity, NPH in children presents similar renal and extrarenal manifestations, thus suggesting the involvement of common pathological routes.

Original languageEnglish
Pages (from-to)44-51
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume35
Issue number1
Publication statusPublished - 2000

Fingerprint

Italy
Kidney
Retinal Degeneration
Genetic Association Studies
Dialysis
Genetic Heterogeneity
Gene Deletion
Research
Point Mutation
Liver Cirrhosis
Chronic Kidney Failure
Exons
Familial juvenile Nephronophthisis
Survival
Population
Genes

Keywords

  • Chronic renal failure
  • Nephrocystin
  • Nephronophthisis

ASJC Scopus subject areas

  • Nephrology

Cite this

Clinical and molecular heterogeneity of juvenile nephronophthisis in Italy : Insights from molecular screening. / Caridi, Gianluca; Dagnino, Monica; Gusmano, Rosanna; Ginevri, Fabrizio; Murer, Luisa; Ghio, Luciana; Piaggio, Giorgio; Ciardi, Maria Rosa; Perfumo, Francesco; Ghiggeri, Gian Marco.

In: American Journal of Kidney Diseases, Vol. 35, No. 1, 2000, p. 44-51.

Research output: Contribution to journalArticle

Caridi, Gianluca ; Dagnino, Monica ; Gusmano, Rosanna ; Ginevri, Fabrizio ; Murer, Luisa ; Ghio, Luciana ; Piaggio, Giorgio ; Ciardi, Maria Rosa ; Perfumo, Francesco ; Ghiggeri, Gian Marco. / Clinical and molecular heterogeneity of juvenile nephronophthisis in Italy : Insights from molecular screening. In: American Journal of Kidney Diseases. 2000 ; Vol. 35, No. 1. pp. 44-51.
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AU - Caridi, Gianluca

AU - Dagnino, Monica

AU - Gusmano, Rosanna

AU - Ginevri, Fabrizio

AU - Murer, Luisa

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AU - Piaggio, Giorgio

AU - Ciardi, Maria Rosa

AU - Perfumo, Francesco

AU - Ghiggeri, Gian Marco

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