Article Figures & Data
Figures
- Figure 1.
Physical map of the human NPHP3 (a through c) and the mouse pcy (d) loci. (a) Polymorphic markers and sequence-tagged sites in the NPHP3 region. Flanking markers are D3S1292 and D3S1238. Gene symbols are given in parenthesis. Expressed sequence-tagged sites (EST) are shown in italics. (b) Complete yeast artificial chromosomes (YAC) contig generated in the region. Sequence-tagged site (STS) content for markers in (a) is indicated by vertical lines and dots on YAC clones. (c) PAC and BAC in the region. STS content for markers in (a) is indicated by vertical lines and triangles. PAC or BAC with asterisks were studied by fluorescence in situ hybridization (FISH) and are located on human chromosome 3q21 to q22. (d) Whitehead YAC contig (WC9.35) on mouse chromosome 9 of the pcy locus with EST markers showing homology to genes identified in the human NPHP3 region. The minimal syntenic region of NPHP3 and pcy is shown hatched. The centromeric (cen) to telomeric (tel) orientation is indicated.
- Figure 2.
FISH mapping of PAC clone 286D11 (alias D11286) on human chromosome 3q21 to q22.
- Figure 3.
Haplotype analyses of new probands ID213 and ID202 from the large Venezuelan adolescent nephronophthisis (NPH3) kindred. Note that both probands homozygously share the same haplotype that is associated with the affected status of the Venezuelan kindred studied (2). For comparison, haplotypes of three previously reported individuals are shown, one affected proband and one obligate carrier, in whom recombinations for markers D3S1292 and D3S1238, respectively, define the critical region of NPH3 (underlined). The centromeric (cen) to telomeric (tel) orientation is indicated.
- Figure 4.
Renal ultrasound of proband ID213 showing a right kidney (A) with a length of 7.6 cm and a left kidney (B) measuring 8.3 cm. Kidneys have increased echogenicity and multiple cysts ranging in size from 0.2 to 2.0 cm in diameter. (C) Cross section of a 2-wk-old pcy mouse showing cysts located predominantly at the corticomedullary junction and in the medulla. (D) Silver-methenamine trichrome staining of a renal biopsy of proband ID213 with typical findings for NPH3 consisting of tubular basement membranes changes with segments of thickening, thinning, folding and a multilayered appearance, tubular atrophy and dilation, mononuclear infiltrates, and diffuse interstitial fibrosis. (E) Periodic acid-Schiff staining of renal specimen of a 2-mo-old pcy mouse exhibiting similar findings as observed in NPH3, consisting of tubular atrophy and dilation, mononuclear infiltrates, and diffuse interstitial fibrosis.
Tables
- Table 1.
Results of sequence similarity analysis using murine EST and genes located in the vicinity of the pcy locusa
Mouse EST or Gene Homologous Human EST or Geneb Sequence Identity aEST, expressed sequence-tagged site. bAll human homologous EST and genes that were identified are located within the critical region of NPHP3 (see Figure 1), demonstrating synteny of the human NPHP3 and the murine pcy locus. D9Mit24, trf (transferrin) TF (transferrin) 94/115 (81%) 04.MMHAP88FRB7.seq SLC21a2 (prostaglandin transporter) 111/127 (87%) D18389, EST-cluster Mm. 1687 TOPBP1 280/327 (85%) R74726 EST cluster Hs. 103379 (WI-15706) 169/191 (88%) - Table 2.
Comparison of clinical, pathological, and genetic findings of adolescent NPH and polycystic kidney disease in mice (pcy)a
Adolescent NPH Polycystic Kidney Disease (pcy) aNPH, nephronophthisis. Inheritance Autosomal recessive Autosomal recessive Manifestation of renal failure Late (median age, 19 yr) Late (adult mice) Range of age at renal failure Wide range (12 to 47 yr) Wide range depending on genetic background Renal cyst location Predominantly at the corticomedullary junction In the beginning at the corticomedullary junction, later throughout the entire kidney Kidney size Normal or reduced Enlarged Extrarenal disease manifestation Not known Cerebral vascular aneurysms in 12% Histology Tubular basement membrane changes, tubular dilation and atrophy, sclerosing tubulointerstitial nephropathy Tubular basement membrane changes, tubular dilation and atrophy, sclerosing tubulointerstitial nephropathy
