A rare multisystemic disorder with chronic kidney disease: Karyomegalic interstitial nephritis due to homozygous FAN1...

Karyomegalic interstitial nephritis (KIN) is a rare entity associated with biallelic FAN1 (FANCD2/FANCI-Associated Nuclease 1) gene variants. In FAN1-related KIN, abnormal liver function tests and respiratory involvement are common, in addition to chronic kidney disease. Karyomegalic changes have also been reported in many other organs in patients with FAN1-related KIN in various studies. We report the case of a 35-year-old male with chronic kidney disease of unknown aetiology, concurrent recurrent upper and lower respiratory tract infections, and elevated liver function test results with unidentified aetiology. The patient's family history was remarkable for consanguineous parent marriage and history of kidney transplantation in his aunt. A kidney biopsy was performed, which was consistent with KIN. Clinical exome sequencing revealed a homozygous nonsense variant NM_014967.5 (FAN1): c. 2260C > T (p.Arg754Ter). According to the American College of Medical Genetics (ACMG) criteria, this variant is pathogenic and, to the best of our knowledge, has not been previously reported, homozygously. Therefore, the histopathological and clinical diagnoses of KIN were confirmed by genetic studies in our patient. This case report expands the genetic spectrum of FAN1-related KIN, and briefly reviews the current literature data.