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Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical and genetic observations

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An Erratum to this article was published on 01 May 2007

Abstract

Reports on genetically informative steroid-responsive (sensitive) idiopathic nephrotic syndrome (SSNS) families are lacking. We studied an extended SSNS Bedouin (B) family with a high rate of consanguinity. The clinical presentation and steroid response of its 11 affected individuals were similar to those of sporadic SSNS (spontaneous remission towards puberty and minimal change disease by kidney biopsy). Genome-wide linkage analysis, using a 382 microsatellite-markers mapping set and additional markers adjacent to 80 candidate genes of the index family, did not support linkage to any chromosomal locus. Retrospective analysis of all additional children with SSNS treated by our institution in the past 20 years (n = 96, 50% of them of Jewish origin) revealed another five non-related B families with 2–3 first-degree cousins affected with SSNS in each. The overall familial SSNS rate among the B population (excluding the index family) was 28%, compared with 4% among Jews (Js) (OR 1.8–64, P < 0.005). There were more Bs with simple SSNS than there were Js (71% and 40%, respectively; OR 3.58, 95% CI 1.41–9.23, P < 0.01). In summary, SSNS in this index family was not linked to any of the presently known chromosomal loci nor predicted to be caused by mutation in any one of a list of genes associated with nephrotic syndrome (NS). The presence of other B families affected by SSNS supports the role for susceptibility genes enrichment, exposing highly consanguineous populations to an increased incidence of SSNS.

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Abbreviations

B:

bedouin

FSGS:

focal segmental glomerulosclerosis

GBM:

glomerular basement membrane

J:

jew

LOD:

logarithmic odds

MCNS:

minimal change nephrotic syndrome

NS:

nephrotic syndrome

SSNS:

steroid sensitive idiopathic nephrotic syndrome

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Acknowledgment

Dan Geiger’s research was supported by the Israeli Ministry of Science. This study was partially supported by a research grant from the National Institute of Biotechnology in the Negev. We thank Prof. Ilana Shoham-Vardi for her help with the statistical calculations.

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel

    Daniel Landau & Hanna Shalev

  2. Department of Developmental Genetics and Virology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel

    Tal Oved, Luba Abizov & Ruti Parvari

  3. Computer Science Department, Technion, Haifa, Israel

    Dan Geiger

  4. Department of Pediatrics, Soroka Medical Center, P. O. Box 151, Beer Sheva, 84101, Israel

    Daniel Landau & Hanna Shalev

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  1. Daniel Landau
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  2. Tal Oved
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  3. Dan Geiger
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Correspondence to Daniel Landau.

Additional information

An erratum to this article can be found at https://doi.org/10.1007/s00467-007-0448-8

Appendix

Appendix

Tables 2, 3, 4 and 5: markers were used for linkage analysis to the candidate genes. The genetic distance between the gene and the marker was calculated on the basis of the genetic map [37] and the physical distance to the marker in the Human UCSC genome browser https://doi.org/genome.ucsc.edu/cgi-bin/hgGateway), assuming 1 cM equals 0.5 Mb. Candidate genes were chosen on the basis of literature search. A detailed list of the references can be provided by D.L. upon request. See suggested review [38] for podocyte physiology and specific proteins potentially involved in NS. The genes are depicted by categories. Table 2: (a) Hereditary proteinuria syndromes and (b) chromosomal loci linked to NS or other glomerulopathies; Table 3: podocyte-related and GBM structural proteins; Table 4: (a) immunity-related genes, associated with SSNS severity and (b) immunity-related genes, associated with SSNS tendency; Table 5: genes associated with deterioration/fibrosis of renal function (all species).

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Landau, D., Oved, T., Geiger, D. et al. Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical and genetic observations. Pediatr Nephrol 22, 661–669 (2007). https://doi.org/10.1007/s00467-006-0409-7

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