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

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.