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 language | English |
|---|---|
| Pages (from-to) | 44-51 |
| Number of pages | 8 |
| Journal | American Journal of Kidney Diseases |
| Volume | 35 |
| Issue number | 1 |
| Publication status | Published - 2000 |
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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 journal › Article
}
TY - JOUR
T1 - Clinical and molecular heterogeneity of juvenile nephronophthisis in Italy
T2 - Insights from molecular screening
AU - Caridi, Gianluca
AU - Dagnino, Monica
AU - Gusmano, Rosanna
AU - Ginevri, Fabrizio
AU - Murer, Luisa
AU - Ghio, Luciana
AU - Piaggio, Giorgio
AU - Ciardi, Maria Rosa
AU - Perfumo, Francesco
AU - Ghiggeri, Gian Marco
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Chronic renal failure
KW - Nephrocystin
KW - Nephronophthisis
UR - http://www.scopus.com/inward/record.url?scp=0033964719&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033964719&partnerID=8YFLogxK
M3 - Article
C2 - 10620543
AN - SCOPUS:0033964719
VL - 35
SP - 44
EP - 51
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 1
ER -