Skip Navigation


NDT Advance Access originally published online on December 15, 2006
Nephrology Dialysis Transplantation 2007 22(3):772-777; doi:10.1093/ndt/gfl677
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/3/772    most recent
gfl677v2
gfl677v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Karnib, H. H.
Right arrow Articles by Gharavi, A. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Karnib, H. H.
Right arrow Articles by Gharavi, A. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Characterization of a large Lebanese family segregating IgA nephropathy

Hussein H. Karnib1,2, Simone Sanna-Cherchi2, Pierre A. Zalloua1, Walid Medawar1, Vivette D. D’Agati3, Richard P. Lifton4, Kamal Badr1 and Ali G. Gharavi2

1Department of Medicine, American University of Beirut, Beirut, Lebanon, 2Department of Medicine, Division of Nephrology and 3Department of Pathology, Columbia University College of Physician and Surgeons, New York, New York, and 4Department of Genetics and Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA

Correspondence and offprint requests to: Ali G. Gharavi, Department of Medicine, Columbia University College of Physicians and Surgeons, 630 W 168th street, P&S 10-432 New York, New York 10032, USA. Email: ag2239{at}columbia.edu



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 
Background. Familial aggregation of IgA nephropathy (IgAN) suggests that genetic factors contribute to the development of this trait. Because clinical manifestations in IgAN families are often limited to episodic haematuria, large kindreds tractable to linkage analysis have been difficult to identify.

Methods. We identified a large Lebanese-Druze kindred ascertained via an index case with biopsy-documented IgAN. We performed systematic screening of 38 family members and tested linkage to reported IgAN loci.

Results. Screening of this family identified 16 affected individuals, including 2 individuals with biopsy-documented IgAN and 14 with chronic renal failure or abnormal urinalyses on at least three separate occasions. This kindred spanned five generations and contained five consanguineous unions. Multigenerational inheritance suggested that autosomal dominant inheritance was most likely. Phenotypic manifestations among affected individuals varied from isolated haematuria to advanced renal failure necessitating transplantation; one instance of IgAN recurrence after transplantation was also documented. Older age was associated with greater severity of disease and higher incidence of renal failure. Parametric and non-parametric analyses with 33 microsatellite markers did not reveal any evidence of linkage to reported IgAN loci on chromosomes 6q22–23, 2q36 and 4q22–31.

Conclusions. We describe one of the largest multigenerational IgAN kindreds reported to date. The high incidence of renal failure among older generations suggests a significant risk of progression to renal failure. We found no evidence of linkage to known loci, suggesting that familial IgAN encompasses multiple subtypes that will require distinction based on genetic or biomarker data.

Keywords: familial aggregation; IgA nephropathy; linkage analysis



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 
IgA nephropathy [IgAN, online Mendelian inheritance in man (OMIM) #161950] is one of the most common causes for glomerulonephritis and renal failure worldwide [1]. Typical clinical features include haematuria and proteinuria, and episodes of gross haematuria following mucosal infection are common, with nearly 30% of patients developing progressive renal failure [1]. The pathogenesis of this disorder is poorly understood. Demographic and ethnic variation in prevalence, occurrence in identical twins and reports of familial aggregation suggest that genetic factors contribute to the development of this trait [2–4]. However, the identity of specific genes underlying this disorder is not known.

Ascertainment of familial forms of IgAN has been complicated by the requirement for renal biopsy for diagnosis of disease. Moreover, the use of urinalysis screening to classify family members is often suboptimal because urinary findings (such as haematuria) are usually intermittent and necessitate systematic screening at repeated intervals. Nevertheless, we previously ascertained 30 small- to medium-sized IgAN families, which enabled us to identify a locus on chromosome 6q22–23 [5], with 60% of kindreds showing linkage to this locus under an autosomal dominant model with reduced penetrance [5]. More recently, other genome-wide screens have confirmed genetic heterogeneity and reported susceptibility loci on chromosomes 2q36 and 4q22–31 [6,7]. These data indicate that the diagnosis of IgAN may encompass several subtypes that are not distinguishable on the basis of renal biopsy or clinical findings alone. Here, we characterize a large Lebanese-Druze IgAN kindred in which family members manifest a high penetrance of haematuria and/or renal failure, constituting one of the largest multigenerational kindreds reported to date.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 Acknowledgements
 References
 
Patient recruitment
The family was ascertained through a biopsy-proven index case. We systematically screened family members by urinalysis, measurement of serum chemistries or chart review. We applied the criteria used in our initial linkage study to assign affection status [5]. Relatives were classified as affected if they had renal biopsy findings diagnostic for IgAN, which was defined pathologically as dominant or codominant glomerular staining for IgA and histological evidence of mesangial proliferation or expansion. A clinical diagnosis of glomerulonephritis was made based on the presence of haematuria [>5 red blood cells (rbc)/hpf] and/or proteinuria (>30 mg/dl on urine dipstick) on at least three occasions spaced >3 weeks apart, or stage III chronic kidney disease (CKD) or worse without other identifiable causes such as diabetes. Several deceased individuals were considered as probably affected based on a history of chronic renal failure (stage III CKD or worse) without other attributable cause. As before, relatives with normal urinalysis, no history of renal disease and aged >40 years were classified as unaffected. All other individuals were classified as phenotype unknown. The study protocol was approved by the Institutional Review Board at the American University of Beirut and the Western Institutional Review Board for Columbia University. Participating subjects provided written informed consent.

Genotyping
Genomic DNA was extracted from peripheral blood using standard methods. To test linkage to candidate loci, we genotyped 33 highly polymorphic microsatellite markers spanning chromosomes 6q22–23, 2q36 and 4q22–31. These markers were selected from the genome-wide panel of the Marshfield Weber set 13 (http://www.marshfieldclinic.org) and the panel previously utilized to localize the IGAN1 locus [5]. Fluorescent dye-labelled primers were used to direct PCR at microsatellite loci (primer sequences available on request). PCR products were resolved on a capillary sequencer (SpectruMedix LLC, State College, PA, USA), and genotypes were scored using the GenoSpectrumV220 software (SpectruMedix LLC).

Analysis of linkage
We performed pair-wise and multipoint analysis of linkage using the FASTLINK 4.1 and Allegro 1.2 programs, respectively [8,9]. Parametric analysis was performed under the model previously used to map the IGAN1 locus [5]. We performed affected-only analysis specifying autosomal-dominant inheritance, disease gene frequency of 0.001, and a phenocopy rate of 0.01. Allele frequencies were calculated based on the frequencies observed in the data set. In addition, we also performed non-parametric, allele-sharing analysis using Allegro 1.2. Published significance thresholds were used [11,12]. Power analyses were performed with 500 simulations of genotypes using the same family structure and affection status as our pedigree, and specifying a 20-cM genetic map with marker spacing and heterozygosities equivalent to those used at our candidate intervals.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 Acknowledgements
 References
 
Clinical characterization
The family was ascertained through a 60-year-old Druze male who presented in 2005 for evaluation of renal allograft dysfunction to the American University Hospital, a large tertiary care medical centre in Beirut. In 1992, the patient had presented with end-stage renal failure of unknown aetiology at another Lebanese hospital, necessitating a living, related kidney transplant from an HLA-matched brother. A few months after transplantation, renal function was normal but he developed persistent haematuria. An allograft biopsy was performed, revealing segmental to global mesangial hypercellularity, without evidence of tubular atrophy, interstitial fibrosis, inflammation or tubulitis. The immunofluorescence panel revealed mesangial staining for IgA only; stains for IgG, IgM, C3, C4 and fibrin were negative. The patient was diagnosed with recurrent IgA nephropathy, which was considered to be a recurrence of his native kidney disease. EM studies were not performed in the allograft biopsy. This diagnosis was confirmed after review of the allograft biopsy sections at Columbia University in 2005. The proband continued to have microscopic haematuria and episodic gross haematuria. On evaluation at the American University Hospital, he showed persisting haematuria with proteinuria <1g/24 h and a creatinine of 1.8 mg/dl. He was continued on a regimen of ciclosporin and atenolol and has maintained stable renal function on follow-up.

The proband provided a significant family history (Table 1, Figure 1). An older brother (ID# 61) had also been diagnosed with IgAN by renal biopsy when he presented 13 years earlier with persistent microscopic haematuria, proteinuria and renal insufficiency (creatinine 1.6 mg/dl). EM studies were not available to evaluate the thickness of glomerular basement membranes. This individual now has advanced renal failure (creatinine 6.0 mg/dl) necessitating renal replacement therapy. Furthermore, two siblings (ID# 54, 59) had been known to have persistent microhaematuria, first detected when they underwent screening as prospective kidney donors. Finally, the proband's mother, maternal aunts and uncles had a history of renal dysfunction without obvious predisposing cause such as long-standing diabetes or hypertension.


View this table:
[in this window]
[in a new window]

  		Table 1. Clinical data in individuals screened

 

Figure 1
View larger version (29K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1. The structure of the Lebanese Druze kindred is shown. The symbols are defined in the box. Phenotype details and classification criteria are described in Table 1 and ‘Methods’. Asterists indicate individuals who underwent screening and provided blood samples. The proband is indicated by the arrow.

 
This striking family history initiated a prospective screening of family members to detect additional affected individuals. Family members were screened at the clinical research unit in the American University Hospital or during home visits. Medical charts were reviewed whenever available to obtain further clinical information. All family members resided in the same village in the Druze community 50 km southeast of Beirut. In total, we screened 38 subjects and identified 16 affected individuals: two individuals had biopsy-documented IgAN (the index case ID#55 and his brother, # 61). Thirteen individuals were classified as affected based on persisting abnormal urinalyses (2 with haematuria plus proteinuria and 11 with haematuria only); these individuals all had >10 rbc/hpf on three separate occasions. One individual (ID# 39) was classified as affected based on end-stage renal disease (ESRD) with unknown aetiology necessitating living, related kidney transplant. He had normal renal function and urinalysis at the time of screening. In addition, medical histories revealed that six deceased individuals in the older generations (ID# 10, 11, 14, 15, 18 and 23) had a history of advanced renal failure with no other attributable factors such as diabetes. Finally, 22 individuals had normal urinalyses: 8 were classified as unaffected and 14 as phenotype unknown (12 with negative urinary finding and aged <40 years; 1 with incomplete workup; 1 with haematuria on the first screening but subsequently normal urinalyses).

The affected individuals included nine males and seven females, with a mean age of 45.7 years at diagnosis (range 13–79 years). Of these, six individuals were previously unaware of abnormal urine sediments and were referred for further workup subsequent to our screening programme. As in our previous study [5], we also defined a sub-category of affected individuals with more severe clinical manifestations (episodic macrohaematuria, proteinuria or chronic renal failure/transplantation). Individuals in this group (ID #20, 39, 40, 55, 59, 61, 65, 81) were older compared with the remaining affected subjects who only had isolated haematuria or unaffected family members, suggesting a risk of disease progression with older age [mean age 56 vs 36 vs 33 years, respectively, analysis of variance (ANOVA) P = 0.03)]. This was also consistent with the finding that six deceased individuals in older generations had a history of advanced kidney failure.

This extended kindred spanned five generations and contained five consanguineous unions (Figure 1). Because consanguinity is common in the Druze population [10], this did not automatically imply autosomal recessive inheritance. Rather, multigenerational inheritance was noted, and affected individuals were present both among offspring of consanguineous and non-consanguineous unions, arguing against a simple recessive model. Sex-linked inheritance was unlikely because male-to-male transmission was observed. Altogether, the pattern of transmission was most consistent with autosomal dominant inheritance or multifactorial causation.

Analysis of linkage to candidate loci
Our previous studies had provided evidence for a major locus for familial IgAN on chromosome 6q22–23 [5]; new susceptibility loci have recently been reported on chromosomes 2q36 and 4q22–31 [6,7]. To determine whether disease in this family was attributable to genetic variation at these intervals, we performed analysis of linkage after typing 33 microsatellite markers across these loci. We performed pair-wise and multipoint parametric analyses classifying the eight patients as affected with more severe manifestation of disease and counting all other individuals as unknown. The rationale for applying this more stringent phenotype was to avoid erroneous rejection of linkage due to phenotyping error or presence of phenocopy. In addition, trimming of the pedigree structure enabled omission of consanguinity loops which can complicate parametric analysis, but still maintained sufficient power to detect linkage with genome-wide significance. Simulations, using this most stringent phenotypic classification and affected only analysis, predicted a maximum expected LOD score of 3.2 (average 2.4 ± 1.2) under an autosomal dominant model.

We found no evidence of linkage to the three-candidate loci tested, with LOD scores <–2 across most of the regions surveyed. These data indicated that variation at these intervals do not contribute to disease in this family. Modification of allele frequency or linkage parameters had negligible effects on these results. Moreover, there was no evidence of linkage using non-parametric allele sharing methods, demonstrating that absence of linkage was not due to misspecification of disease model (best statistic NPL = 0.6, P = 0.2 at D2S247). These data demonstrate that genes located outside the tested intervals contribute to disease in our family.



   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
Acknowledgements
 References
 
As exemplified in studies of familial focal segmental glomerulosclerosis, single large kindreds are extremely valuable for clarifying the genetic basis of heterogeneous disorders [12,13]. Here, we report a uniquely large kindred with familial IgAN ideally suited to achieve chromosomal localization of trait loci. Systematic screening led to the identification of 16 affected individuals: the phenotypes documented in this study are quite robust, since haematuria was documented on three successive occasions and all affected individuals manifested >10 rbc/hpf on urinalysis. The high penetrance of persistent haematuria was the most striking finding in this pedigree. Otherwise, the clinical spectrum of disease varied considerably between affected individuals, ranging from asymptomatic haematuria to macrohaematuria, proteinuria or severe nephropathy necessitating renal transplantation. Post-transplant recurrence of IgAN was also documented, and was instructive as this implicates an extra-renal defect in this family. The other interesting finding concerned the association of older age with more severe phenotype. Particularly, if the six deceased individuals with a history of kidney failure are considered as affected, there was a high incidence of renal failure (10/22 affected, 45%) in older affected subjects, suggesting a high risk of progression to ESRD in this family. These findings suggest that the risk of renal failure is age-dependent and may be particularly high in specific subsets of IgAN families, providing a potential explanation for discordant findings about the outcome of familial vs sporadic forms of IgAN [14,15].

Consistent with previous reports of familial IgAN, multigenerational inheritance and male-to-male transmission suggested that autosomal dominant inheritance was most likely. We excluded linkage to the IGAN1 locus on chromosome 6q22–23 and to the recently reported loci on chromosomes 2q36 and 4q22–31. The chromosome 2q36 region encompasses the collagen genes implicated in thin basement membrane disease [16], a dominant trait associated with a high incidence of haematuria but low risk of renal failure [17]. Although EM studies were not available to study the thickness of basement membranes, the presence of two individuals with biopsy-documented IgAN, the high prevalence of renal failure and the negative linkage at 2q36, all support the diagnosis of familial IgAN in our Lebanese kindred. We have now embarked on a genome scan in this pedigree to search for a new locus for IgAN. We are also revisiting this kindred to further characterize additional family members by non-invasive testing and perform renal biopsy with EM studies in individuals in whom this procedure is clinically indicated. Furthermore, this kindred originates from the Druze community in Lebanon [18], a religious isolate dating back to the 11th century. Marriage within the community is strongly encouraged and consanguineous unions are common, as in most Arab populations [10,19]. Because of this population structure, founder mutations for several Mendelian disorders have been reported in Druze population [20,21]. Hence, the possibility of founder alleles for IgAN in the Druze community deserves further exploration as additional IgAN patients with sporadic or familial disease could greatly facilitate gene identification by disequilibrium mapping.

Like most complex traits, clinical manifestations of IgAN are likely determined by the interplay between genetic and environmental factors. Familial forms of IgAN represent populations enriched for genetic contributions to disease, thereby simplifying the search for major aetiologic factors. Nonetheless, our data confirm that even familial IgAN encompasses multiple subtypes that will require classification based on biomarker or genetic profile [5–7]. It is also noteworthy that despite similarity in genetic background, geographic residence and lifestyle, there was great variability in manifestations of disease among pedigree members. Although some well-known environmental insults, such as viral infections, can trigger or exacerbate IgAN, we could not identify any single common environmental exposure that contributed to disease in our pedigree. The reasons underlying variation in incidence and clinical presentation of IgAN are presently not well understood. Moreover, the relationship of familial IgAN to the sporadic forms of disease remains to be clarified. Once specific genetic, physiological or environmental aetiologic factors have been identified, one may be able to better stratify patients and dissect the interactions between environment and genotype.

For now, our data have significant implications for design and execution of genetic studies of IgAN. Because as many as four loci may be involved, these data suggest that large cohorts or uniquely large kindreds will be required for successful identification of underlying genes. Studies of familial IgAN can be further facilitated by genealogical investigation of sporadic IgAN among isolated populations. This approach was pioneered by Julian et al. [22] and Wyatt et al. [23] who reported common ancestry among two-thirds of IgAN patients originating from Central and Eastern Kentucky, a population that has characteristics of a genetic isolate [22,23]. Using similar approaches, Izzi et al. [24] recently showed that patients with glomerulonephritis originating from isolated villages from Northern Italy could be traced back to common ancestors in the 16th and 17th centuries, enabling the construction of three large pedigrees. Together with investigation of large Mendelian kindreds, studies of such populations should help clarify the pathogenesis of IgAN and improve diagnostic and therapeutic options.



   Acknowledgements
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
References
 
The authors would like to thank the patients and family members for participating in this study. They also thank Bruce Julian for helpful discussions. The study was supported in part by NIH 1P01DK61525-01. H.H.K. is supported by an ISN International Fellowship Program. A.G.G. is supported by the Emerald Foundation and the National Kidney Foundation Clinical Scientist Program.

Notes added in Proof. A new suggestive locus on chr. 17q was recently reported by Bisceglia et al. [7]. We are currently evaluating this interval in our IgAN family.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Acknowledgements
 References
 

  1. Barratt J and Feehally J. (2005) IgA nephropathy. J Am Soc Nephrol 16:2088–2097.[Free Full Text]
  2. Galla JH, Kohaut EC, Alexander R, et al. (1984) Racial difference in the prevalence of IgA-associated nephropathies. Lancet 2:522.[Web of Science][Medline]
  3. Scolari F. (1999) Familial IgA nephropathy. J Nephrol 12:213–219.[CrossRef][Web of Science][Medline]
  4. Levy M. (1993) Multiplex families in IgA nephropathy. Contrib Nephrol 104:46–53.[Medline]
  5. Gharavi AG, Yan Y, Scolari F, et al. (2000) IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nat Genet 26:354–357.[CrossRef][Web of Science][Medline]
  6. Pei YPA, Magistroni R, Klassen J, Kappel J, Cattran D, St George P. (2005) Localization of a novel disease susceptibility locus to chromosome 2q36 by genome scan of a large extended Canadian family with IgA nephropathy (IgAN). J Am Soc Nephrol 16:Suppl S, 592A.
  7. Bisceglia L, Cerullo G, Forabosco P, et al. (2006) Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci. Am J Hum Genet 79:1130–1134.[CrossRef][Web of Science][Medline]
  8. Cottingham RW Jr, Idury RM, Schaffer AA. (1993) Faster sequential genetic linkage computations. Am J Hum Genet 53:252–263.[Web of Science][Medline]
  9. Gudbjartsson DF, Jonasson K, Frigge ML, et al. (2000) Allegro, a new computer program for multipoint linkage analysis. Nat Genet 25:12–13.[CrossRef][Web of Science][Medline]
  10. Vardi-Saliternik R, Friedlander Y, Cohen T. (2002) Consanguinity in a population sample of Israeli Muslim Arabs, Christian Arabs and Druze. Ann Hum Biol 29:422–431.[CrossRef][Web of Science][Medline]
  11. Lander E and Kruglyak L. (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11:241–247.[CrossRef][Web of Science][Medline]
  12. Kaplan JM, Kim SH, North KN, et al. (2000) mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 24:251–256.[CrossRef][Web of Science][Medline]
  13. Winn MP, Conlon PJ, Lynn KL, et al. (2005) A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 308:1801–1804.[Abstract/Free Full Text]
  14. Schena FP, Cerullo G, Rossini M, et al. (2002) Increased risk of end-stage renal disease in familial IgA nephropathy. J Am Soc Nephrol 13:453–460.[Abstract/Free Full Text]
  15. Izzi C, Ravani P, Torres D, et al. (2006) IgA nephropathy: the presence of familial disease does not confer an increased risk for progression. Am J Kidney Dis 47:761–769.[CrossRef][Web of Science][Medline]
  16. Buzza M, Dagher H, Wang YY, et al. (2003) Mutations in the COL4A4 gene in thin basement membrane disease. Kidney Int 63:447–453.[CrossRef][Web of Science][Medline]
  17. Nieuwhof CM, de Heer F, de Leeuw P, et al. (1997) Thin GBM nephropathy: premature glomerular obsolescence is associated with hypertension and late onset renal failure. Kidney Int 51:1596–1601.[Web of Science][Medline]
  18. Der Kaloustian VM. (1997) Genetic Diseases in Lebanon. Genetic Disorders Among Arab populations(Oxford University Press, New York) pp. 260–289.
  19. Barbari A, Stephan A, Masri M, et al. (2003) Consanguinity-associated kidney diseases in Lebanon: an epidemiological study. Mol Immunol 39:1109–1114.[CrossRef][Web of Science][Medline]
  20. Touitou I, Ben-Chetrit E, Notarnicola C, et al. (1998) Familial Mediterranean fever clinical and genetic features in Druzes and in Iraqi Jews: a preliminary study. J Rheumatol 25:916–919.[Web of Science][Medline]
  21. Mandel H, Szargel R, Labay V, et al. (2001) The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat Genet 29:337–341.[CrossRef][Web of Science][Medline]
  22. Julian BA, Quiggins PA, Thompson JS, et al. (1985) Familial IgA nephropathy. Evidence of an inherited mechanism of disease. N Engl J Med 312:202–208.[Abstract]
  23. Wyatt RJ, Rivas ML, Julian BA, et al. (1987) Regionalization in hereditary IgA nephropathy. Am J Hum Genet 41:36–50.[Web of Science][Medline]
  24. Izzi C, Sanna-Cherchi S, Prati E, et al. (2006) Familial aggregation of primary glomerulonephritis in an Italian population isolate: Valtrompia study. Kidney Int 69:1033–1040.[CrossRef][Web of Science][Medline]
Received for publication: 30. 8.06
Accepted in revised form: 19.10.06


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
A. D. Paterson, X.-Q. Liu, K. Wang, R. Magistroni, X. Song, J. Kappel, J. Klassen, D. Cattran, P. St. George-Hyslop, and Y. Pei
Genome-Wide Linkage Scan of a Large Family with IgA Nephropathy Localizes a Novel Susceptibility Locus to Chromosome 2q36
J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2408 - 2415.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/3/772    most recent
gfl677v2
gfl677v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Karnib, H. H.
Right arrow Articles by Gharavi, A. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Karnib, H. H.
Right arrow Articles by Gharavi, A. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?