Top

Published in:

01-05-2007 | Original Article

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

Authors: Daniel Landau, Tal Oved, Dan Geiger, Luba Abizov, Hanna Shalev, Ruti Parvari

Published in: Pediatric Nephrology | Issue 5/2007

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.

Available only for authorised users

White RH (1973) The familial nephrotic syndrome. I: A European survey. Clin Nephrol 1:215–219PubMed

Kestila M, Lenkkeri U, Mannikko M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K (1998) Positionally cloned gene for a novel glomerular protein—nephrin—is mutated in congenital nephrotic syndrome. Mol Cell 1:575–582CrossRefPubMed

Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler MC, Niaudet P, Antignac C (2000) NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 24:349–354CrossRefPubMed

Zenker M, Aigner T, Wendler O, Tralau T, Muntefering H, Fenski R, Pitz S, Schumacher V, Royer-Pokora B, Wuhl E, Cochat P, Bouvier R, Kraus C, Mark K, Madlon H, Dotsch J, Rascher W, Maruniak-Chudek I, Lennert T, Neumann LM, Reis A (2004) Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum Mol Genet 13:2625–2632CrossRefPubMed

Fuchshuber A, Gribouval O, Ronner V, Kroiss S, Karle S, Brandis M, Hildebrandt F (2001) Clinical and genetic evaluation of familial steroid-responsive nephritic syndrome in childhood. J Am Soc Nephrol 12:374–378PubMed

Negev Development Authority and Negev Center for Regional Development, Ben Gurion University. Statistical Report. https://doi.org/www.negev.co.il/statis/ch2.asp

Barratt TM, Avner ED, Harmon WE (1999) Pediatric nephrology, 4th edn. Lippincott, Williams & Wilkins, Baltimore, pp 731–747

Statistical abstract of Israel No. 57, CBS, Central Bureau of Statistics, Jerusalem, 2006 https://doi.org/www1.cbs.gov.il/reader/shnatonenew_site.htm

Fishelson M, Geiger D (2002) Exact genetic linkage computations for general pedigrees. Bioinformatics 18(Suppl 1):S189–198CrossRefPubMed

10.

Shalhoub RJ (1974) Pathogenesis of lipid nephrosis: a disorder on T-cell function. Lancet 2:556–560CrossRefPubMed

11.

Yoshizawa N, Kusumi Y, Matsumoto K, Oshima S, Takeuchi A, Kawamura O, Kubota T, Kondo S, Niwa H (1989) Studies of a glomerular permeability factor in patients with minimal-change nephrotic syndrome. Nephron 51:370–376CrossRefPubMed

12.

Schnaper HW, Aune TM (1987) Steroid-sensitive mechanism of soluble immune response suppressor production in steroid-responsive nephrotic syndrome. J Clin Invest 79:257–264CrossRefPubMedPubMedCentral

13.

Savin VJ, Sharma R, Sharma M, McCarthy ET, Swan SK, Ellis E, Lovell H, Warady B, Gunwar S, Chonko AM, Artero M, Vincenti F (1996) Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med 334:878–883CrossRefPubMed

14.

Le Berre L, Godfrin Y, Gunther E, Buzelin F, Perretto S, Smit H, Kerjaschki D, Usal C, Cuturi C, Soulillou JP, Dantal J (2002) Extrarenal effects on the pathogenesis and relapse of idiopathic nephrotic syndrome in Buffalo/Mna rats. J Clin Invest 109:491–498CrossRefPubMedPubMedCentral

15.

Grimbert P, Audard V, Remy P, Lang P, Sahali D (2003) Recent approaches to the pathogenesis of minimal-change nephrotic syndrome. Nephrol Dial Transplant 18:245–248CrossRefPubMed

16.

Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, Rastaldi MP, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler M, Davidson A, Sugimoto H, Kalluri R, Sharpe AH, Kreidberg JA, Mundel P (2004) Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 113:1390–1397CrossRefPubMedPubMedCentral

17.

Ruf RG, Schultheiss M, Lichtenberger A, Karle SM, Zalewski I, Mucha B, Everding AS, Neuhaus T, Patzer L, Plank C, Haas JP, Ozaltin F, Imm A, Fuchshuber A, Bakkaloglu A, Hildebrandt F; APN Study Group (2004) Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome. Kidney Int 66:564–570CrossRefPubMed

18.

Sako M, Nakanishi K, Obana M, Yata N, Hoshii S, Takahashi S, Wada N, Takahashi Y, Kaku Y, Satomura K, Ikeda M, Honda M, Iijima K, Yoshikawa N (2005) Analysis of NPHS1, NPHS2, ACTN4, and WT1 in Japanese patients with congenital nephrotic syndrome. Kidney Int 67:1248–1255CrossRefPubMed

19.

Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, Mathis BJ, Rodriguez-Perez JC, Allen PG, Beggs AH, Pollak MR (2000) Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 24:251–256CrossRefPubMed

20.

Boner G, Cox AJ, Kelly DJ, Tobar A, Bernheim J, Langham RG, Cooper ME, Gilbert RE (2003) Does vascular endothelial growth factor (VEGF) play a role in the pathogenesis of minimal change disease? Nephrol Dial Transplant 18:2293–2299CrossRefPubMed

21.

Noakes PG, Miner JH, Gautam M, Cunningham JM, Sanes JR, Merlie JP (1995) The renal glomerulus of mice lacking s-laminin/laminin beta 2: nephrosis despite molecular compensation by laminin beta 1. Nat Genet 10:400–406CrossRefPubMed

22.

Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O, Miner JH, Shaw AS (1999) Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science 286:312–315CrossRefPubMed

23.

Clark AG, Vaughan RW, Stephens HA, Chantler C, Williams DG, Welsh KI (1990) Genes encoding the beta-chains of HLA-DR7 and HLA-DQw2 define major susceptibility. Clin Sci (Lond) 78:391–397CrossRef

24.

Tain YL, Liu CA, Yang KD (2002) Implications of blood soluble and cell surface tumor necrosis factor receptors in childhood nephrotic syndrome. Pediatr Nephrol 17:926–932CrossRefPubMed

25.

Uemichi T, Liepnieks JJ, Benson MD (1994) Hereditary renal amyloidosis with a novel variant fibrinogen. J Clin Invest 93:731–736CrossRefPubMedPubMedCentral

26.

Costa PP, Figueira AS, Bravo FR (1978) Amyloid fibril protein related to prealbumin in familial amyloidotic polyneuropathy. Proc Natl Acad Sci USA 75:4499–4503CrossRefPubMedPubMedCentral

27.

Pickering MC, Cook HT, Warren J, Bygrave AE, Moss J, Walport MJ, Botto M (2002) Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. Nat Genet 31:424–428CrossRefPubMed

28.

Neuhausen SL, Weizman Z, Camp NJ, Elbedour K, Sheffield VC, Zone JJ, Carmi R (2002) HLA-DQA1-DQB1 genotypes in Bedouin families with celiac disease. Hum Immunol 63:502–507CrossRefPubMed

29.

Alsana F, Porath A, Binsztok M, Weizman Z (2000) Factors affecting the incidence of celiac disease in two different populations. J Pediatr Gastroenterol Nutr 31:S211

30.

Neuhausen SL, Feolo M, Camp NJ, Farnham J, Book L, Zone JJ (2002) Genome-wide linkage analysis for celiac disease in North American families. Am J Med Genet 111:1–9CrossRefPubMed

31.

Peltonen L, Palotie A, Lange K (2000) Use of population isolates for mapping complex traits. Nat Rev Genet 1:182–190CrossRefPubMed

32.

Weitzman D, Shoham-Vardi I, Elbedour K, Belmaker I, Siton Y, Carmi R (2000) Factors affecting the use of prenatal testing for fetal anomalies in a traditional society. Community Genet 3:61–70

33.

Zlotogora J (2002) Molecular basis of autosomal recessive diseases among the Palestinian Arabs. Am J Med Genet 109:176–182CrossRefPubMed

34.

Zlotogora J, Shalev S, Habiballah H, Barjes S (2000) Genetic disorders among Palestinian Arabs: 3. Autosomal recessive disorders in a single village. Am J Med Genet 92:343–345CrossRefPubMed

35.

Ombra MN, Forabosco P, Casula S, Angius A, Maestrale G, Petretto E, Casu G, Colussi G, Usai E, Melis P, Pirastu M (2001) Identification of a new candidate locus for uric acid nephrolithiasis. Am J Hum Genet 68:1119–1129CrossRefPubMedPubMedCentral

36.

Ruf RG, Fuchshuber A, Karle SM, Lemainque A, Huck K, Wienker T, Otto E, Hildebrandt F (2003) Identification of the first gene locus (SSNS1) for steroid-sensitive nephrotic syndrome on chromosome 2p. J Am Soc Nephrol 14:1897–1900CrossRefPubMed

37.

Kong X, Murphy K, Raj T, He C, White PS, Matise TC (2004) A combined linkage-physical map of the human genome. Am J Hum Genet 75:1143–1148CrossRefPubMedPubMedCentral

38.

de Zoysa JR, Topham PS (2005) Podocyte biology in human disease. Nephrology 10:362–367CrossRefPubMed

Title: Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical and genetic observations
Authors: Daniel Landau
Tal Oved
Dan Geiger
Luba Abizov
Hanna Shalev
Ruti Parvari
Publication date: 01-05-2007
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 5/2007
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-006-0409-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2007

Renal scarring sequelae in childhood Kawasaki disease

Ceftriaxone associated nephrolithiasis: a prospective study in 284 children

Nine novel COL4A3 and COL4A4 mutations and polymorphisms identified in inherited membrane diseases

Effects of deflazacort vs. methylprednisone: a randomized study in kidney transplant patients

Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis

Severe anemia caused by the angiotensin receptor blocker irbesartan after renal transplantation