PMID- 10620543
OWN - NLM
STAT- MEDLINE
DCOM- 20000112
LR  - 20220129
IS  - 1523-6838 (Electronic)
IS  - 0272-6386 (Linking)
VI  - 35
IP  - 1
DP  - 2000 Jan
TI  - Clinical and molecular heterogeneity of juvenile nephronophthisis in Italy: 
      insights from molecular screening.
PG  - 44-51
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 prompted 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.
FAU - Caridi, G
AU  - Caridi G
AD  - Laboratory and Department of Nephrology, G. Gaslini Institute, Genoa, Italy.
FAU - Dagnino, M
AU  - Dagnino M
FAU - Gusmano, R
AU  - Gusmano R
FAU - Ginevri, F
AU  - Ginevri F
FAU - Murer, L
AU  - Murer L
FAU - Ghio, L
AU  - Ghio L
FAU - Piaggio, G
AU  - Piaggio G
FAU - Ciardi, M R
AU  - Ciardi MR
FAU - Perfumo, F
AU  - Perfumo F
FAU - Ghiggeri, G M
AU  - Ghiggeri GM
LA  - eng
GR  - E.0770/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Kidney Dis
JT  - American journal of kidney diseases : the official journal of the National Kidney 
      Foundation
JID - 8110075
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (NPHP1 protein, human)
RN  - 0 (Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Aberrations/genetics
MH  - Chromosome Deletion
MH  - Chromosome Disorders
MH  - Chromosomes, Human, Pair 2
MH  - Cytoskeletal Proteins
MH  - Exons
MH  - Female
MH  - Genes, Recessive/genetics
MH  - *Genetic Carrier Screening
MH  - *Genetic Testing
MH  - Genotype
MH  - Humans
MH  - Italy
MH  - Kidney Failure, Chronic/diagnosis/*genetics
MH  - Male
MH  - Membrane Proteins
MH  - Nephritis, Interstitial/diagnosis/*genetics
MH  - Pedigree
MH  - Phenotype
MH  - Point Mutation/genetics
MH  - Proteins/genetics
MH  - Retinitis Pigmentosa/diagnosis/genetics
EDAT- 2000/01/06 00:00
MHDA- 2000/01/06 00:01
CRDT- 2000/01/06 00:00
PHST- 2000/01/06 00:00 [pubmed]
PHST- 2000/01/06 00:01 [medline]
PHST- 2000/01/06 00:00 [entrez]
AID - S0272-6386(00)70300-3 [pii]
AID - 10.1016/S0272-6386(00)70300-3 [doi]
PST - ppublish
SO  - Am J Kidney Dis. 2000 Jan;35(1):44-51. doi: 10.1016/S0272-6386(00)70300-3.