Karyomegalic tubulointerstitial nephritis—A case report

Baba, Füsun; Nanovic, Lisa; Jaffery, Jonathan B.; Friedl, Andreas

doi:10.1016/j.prp.2006.02.004

Cited by 16 publications

(9 citation statements)

References 7 publications

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“…The only distinguishing feature from NPHP in KIN is the presence of karyomegaly (Figure 1b–c), which can also be present in lung, liver, and brain 13 . Currently, 12 families with KIN have been described 10,14 , compatible with autosomal recessive inheritance.…”

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confidence: 99%

“…We then obtained DNA samples from 5 published KIN families and 5 unpublished cases (Table 1). Clinical phenotypes have been published for families A4385 15 , A4393 16 , A1170 10 , A4433 13 , and A4333 14 (Supplementary Table 1). Upon Sanger sequencing of all FAN1 exons, we found 12 different mutations of FAN1 in 9 of the 10 families with KIN (Supplementary Figure 1B, Table 1), detecting both mutated alleles in 9 families (Table 1).…”

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FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

et al. 2012

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SUMMARYChronic kidney disease (CKD) represents a major health burden1. Its central feature of renal fibrosis is not well understood. By whole exome resequencing in a model disorder for renal fibrosis, nephronophthisis (NPHP), we identified mutations of Fanconi anemia-associated nuclease 1 (FAN1) as causing karyomegalic interstitial nephritis (KIN). Renal histology of KIN is indistinguishable from NPHP except for the presence of karyomegaly2. FAN1 has nuclease activity, acting in DNA interstrand crosslinking (ICL) repair within the Fanconi anemia pathway of DNA damage response (DDR)3–6. We demonstrate that cells from individuals with FAN1 mutations exhibit sensitivity to the ICL agent mitomycin C. However, they do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from patients with Fanconi anemia. We complement ICL sensitivity with wild type FAN1 but not mutant cDNA from individuals with KIN. Depletion of fan1 in zebrafish revealed increased DDR, apoptosis, and kidney cysts akin to NPHP. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms of renal fibrosis and CKD.

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FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

et al. 2012

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“…7 Then, a few cases were reported where no familial clustering was identified at all. 8,9,10 Finally, in one case series of three patients with KIN, the author came across a completely different haplotype. However, all three patients in this paper were found to have high serum levels of Ochratoxin.…”

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Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

Chand¹,

Zaka²,

Qin³

2021

Autops Case Rep

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“…Family clustering, highest frequency of the haplotypes HLA A9 B35 and different susceptibility to develop the nephropathy in spite of a high OTA contamination in all subjects support a genetic etiology. Besides, family clustering was reported more than once [2,3,4,8,9,10,25,26,27].…”

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confidence: 99%

New Familial Cases of Karyomegalic Interstitial Nephritis With Mutations in the FAN1 Gene

REJEB

Jerbi

Jilani

et al. 2020

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Karyomegalic interstitial nephritis (KIN) is a rare disease entity that was first described by Burry in 1974 and given this term by Mihatsch 1979 and al five years later. KIN is characterized by chronic tubulo-interstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to progressive decline of renal function. The prevalence of this disease is less than 1% and its pathogenesis is unclear. KIN results from the mutation in the FAN 1 (FANCD2/FANCI-Associated Nuclease 1) gene, a gene involved in the DNA damage response pathway, particularly in the kidney. KIN seems to be rather multifactorial involving an environmental factor Ochratoxin A (OTA) but especially a genetic predisposition. In this article, we report 6 additional cases of KIN with histological evidence in 3 patients. Family clustering and differences in susceptibility to develop the nephropathy in spite of a high OTA contamination in all subjects show that there is a genetic susceptibility. So we completed our explorations by a genetic study. This study allowed us to identify novel mutations in the FAN1 gene in the affected members. To our best knowledge, this is the first Tunisian study involving familial cases of KIN with mutations on the FAN1 gene.

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Karyomegalic tubulointerstitial nephritis—A case report

Cited by 16 publications

References 7 publications

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

New Familial Cases of Karyomegalic Interstitial Nephritis With Mutations in the FAN1 Gene

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Karyomegalic tubulointerstitial nephritis—A case report

Cited by 16 publications

References 7 publications

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

New Familial Cases of Karyomegalic Interstitial Nephritis With Mutations in the FAN1&nbsp;Gene

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New Familial Cases of Karyomegalic Interstitial Nephritis With Mutations in the FAN1 Gene