New familial cases of karyomegalic interstitial nephritis with mutations in the FAN1 gene.

Autor: Rejeb I; Service des Maladies Congénitales et Héréditaires, CHU Mongi Slim La Marsa, La Marsa, Tunisia. imen_rejeb@yahoo.fr., Jerbi M; Service de Néphrologie, CHU Mongi Slim La Marsa, La Marsa, Tunisia.; Laboratory of Renal Pathology LR00SP01, Tunis, Tunisia.; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia., Jilani H; Service des Maladies Congénitales et Héréditaires, CHU Mongi Slim La Marsa, La Marsa, Tunisia.; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia., Gaied H; Service de Néphrologie, CHU Mongi Slim La Marsa, La Marsa, Tunisia.; Laboratory of Renal Pathology LR00SP01, Tunis, Tunisia.; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia., Elaribi Y; Service des Maladies Congénitales et Héréditaires, CHU Mongi Slim La Marsa, La Marsa, Tunisia.; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia., Hizem S; Service des Maladies Congénitales et Héréditaires, CHU Mongi Slim La Marsa, La Marsa, Tunisia.; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia., Aoudia R; Laboratory of Renal Pathology LR00SP01, Tunis, Tunisia.; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia.; Department of Internal Medicine, Charles Nicolle Hospital, Tunis, Tunisia., Hedri H; Laboratory of Renal Pathology LR00SP01, Tunis, Tunisia.; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia.; Department of Internal Medicine, Charles Nicolle Hospital, Tunis, Tunisia., Zaied C; Faculty of Dentistry, Monastir, Tunisia., Abid S; Faculty of Dentistry, Monastir, Tunisia., Bacha H; Faculty of Dentistry, Monastir, Tunisia., BenAbdallah T; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia.; Department of Internal Medicine, Charles Nicolle Hospital, Tunis, Tunisia., BenJemaa L; Service des Maladies Congénitales et Héréditaires, CHU Mongi Slim La Marsa, La Marsa, Tunisia.; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia., Goucha R; Service de Néphrologie, CHU Mongi Slim La Marsa, La Marsa, Tunisia.; Laboratory of Renal Pathology LR00SP01, Tunis, Tunisia.; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia.
Jazyk: angličtina
Zdroj: BMC medical genomics [BMC Med Genomics] 2021 Jun 14; Vol. 14 (1), pp. 160. Date of Electronic Publication: 2021 Jun 14.
DOI: 10.1186/s12920-021-01009-7
Abstrakt: Background: Karyomegalic interstitial nephritis (KIN) is a rare disease entity first described by Burry in 1974. The term KIN was introduced by Mihatsch et al. in 1979. KIN is characterized by chronic tubulointerstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to a progressive decline of renal function. The prevalence of this disease is less than 1% of all biopsies, and its pathogenesis is unclear. KIN results from mutations in FAN1 (FANCD2/FANCI-Associated Nuclease 1), a gene involved in the DNA damage response pathway, particularly in the kidney. In this study, we report two Tunisian consanguineous families with KIN caused by mutations in the FAN1 gene.
Methods: Direct sequencing of the coding regions and flanking intronic sequences of the FAN1 gene was performed in three affected members. Three prediction programs (Polyphen-2 software, SIFT, and MutationTaster) were used to predict the functional effect of the detected variations.
Results: Two causative frameshift variants in the FAN1 gene were identified in each family: The previously described frameshift mutation c.2616delA (p.Asp873ThrfsTer17) and a novel mutation c.2603delT (p.Leu868ArgfsTer22) classified as "pathogenic" according to the American College of Medical Genetics and Genomics (ACMG) guidelines.
Conclusion: To our best knowledge, this is the first Tunisian study involving familial cases of KIN with mutations in the FAN1 gene. We hypothesize that these findings can expand the mutational spectrum of KIN and provide valuable information on the genetic cause of KIN.
Databáze: MEDLINE
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