Genotype-phenotype characteristics and disease progression of FAN1-related karyomegalic tubulointerstitial nephropathy
Abstract
Introduction: Biallelic variants in Fanconi Anemia-associated Nuclease 1 (FAN1) cause karyomegalic tubulointerstitial nephropathy (KIN), a condition poorly characterized in terms of kidney survival, patient survival, and clinical characteristics. Therefore, we undertook a cross-sectional collaborative study to better characterize KIN-FAN1. Methods: To gather data, we distributed a REDCap survey on clinical characteristics and genetic variants of KIN-FAN1 to colleagues and case report authors. Results: Based on the survey, we identified 86 families affected (122 individuals) from 22 countries. There were 56 families (83 individuals) with a genetic diagnosis of KIN-FAN1, including 38 distinct FAN1 variants, and 30 families (39 individuals) with KIN with no predisposing risk factors and without molecular FAN1 testing. The median age at presentation was 38.5 years (interquartile range: 29-43), 62% male. Of the cohort, 46% had asymptomatic elevation of liver function tests, 39% had pulmonary complications, and 6% developed cancer. The median age of kidney failure was 45 years (95% confidence interval (CI): 38-56). Of the cohort, 27.1% died at a median age of 55 years (95% CI: 43-75). Pulmonary complications was/were the cause of death in 15.4% of patients on dialysis and 23.1% of kidney transplant recipients. Compared to other variants, patients with the p.W707X-FAN1 variant were at a significantly higher risk of pulmonary complications (adjusted odds ratio: 8.26 (95% CI: 1.7-40.1) and had a significantly shorter lifespan (hazard ratio: 3.24 (95% CI: 1.13-9.28). No genetic covariates were statistically associated with the progression to kidney failure. Conclusions: Patients with KIN-FAN1 develop kidney failure at a median age of 45 years. Survival is compromised with many dying of pulmonary disease.
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BibTeX
@article{clince2026genotypephenotype,
title = {{Genotype-phenotype characteristics and disease progression of FAN1-related karyomegalic tubulointerstitial nephropathy}},
author = {Michelle Clince and Elhussein A.E. Elhassan and Kendrah Kidd and Emily Malamud and Susan Mcanallen and Arbab Danial and Byung Ha Chung and Myungshin Kim and John Sayer and Intisar Al Alawi and Jelle Bernards and Mouna Jerbi and Rym Goucha and Lamia Ben Jemaa and Imen Rejeb and Chirag Patel and Andrew Mallett and C. John Sperati and Koen de Boeck and Maximilian Müller and Thomas Stehlé and Nisrine Bennani Guebessi and Thomas Robert and Bela Ivanyi and Ildiko Csaszar and Shirlee Shril and Sijie Zheng and Gerry George Mathew and Merve Guzel Dirim and Ahmet Burak Dirim and Laurent Mesnard and Lorraine Gueguen and Franz Schafer and Carsten Bergmann and Daniel Gale and Jan Halbritter and Kathleen Claes and Bertrand Knebelmann and Martina Živná and Stanislav Kmoch and Stanislas Faguer and Friedhelm Hildebrandt and Anthony Bleyer and Peter Conlon},
journal = {Kidney International},
year = {2026},
month = sep,
doi = {10.1016/j.kint.2026.01.001},
url = {https://hal.inrae.fr/hal-05723132v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genotype-phenotype characteristics and disease progression of FAN1-related karyomegalic tubulointerstitial nephropathy
AU - Michelle Clince
AU - Elhussein A.E. Elhassan
AU - Kendrah Kidd
AU - Emily Malamud
AU - Susan Mcanallen
AU - Arbab Danial
AU - Byung Ha Chung
AU - Myungshin Kim
AU - John Sayer
AU - Intisar Al Alawi
AU - Jelle Bernards
AU - Mouna Jerbi
AU - Rym Goucha
AU - Lamia Ben Jemaa
AU - Imen Rejeb
AU - Chirag Patel
AU - Andrew Mallett
AU - C. John Sperati
AU - Koen de Boeck
AU - Maximilian Müller
AU - Thomas Stehlé
AU - Nisrine Bennani Guebessi
AU - Thomas Robert
AU - Bela Ivanyi
AU - Ildiko Csaszar
AU - Shirlee Shril
AU - Sijie Zheng
AU - Gerry George Mathew
AU - Merve Guzel Dirim
AU - Ahmet Burak Dirim
AU - Laurent Mesnard
AU - Lorraine Gueguen
AU - Franz Schafer
AU - Carsten Bergmann
AU - Daniel Gale
AU - Jan Halbritter
AU - Kathleen Claes
AU - Bertrand Knebelmann
AU - Martina Živná
AU - Stanislav Kmoch
AU - Stanislas Faguer
AU - Friedhelm Hildebrandt
AU - Anthony Bleyer
AU - Peter Conlon
PY - 2026
DA - 2026/09/02
JO - Kidney International
DO - 10.1016/j.kint.2026.01.001
UR - https://hal.inrae.fr/hal-05723132v1
AB - Introduction: Biallelic variants in Fanconi Anemia-associated Nuclease 1 (FAN1) cause karyomegalic tubulointerstitial nephropathy (KIN), a condition poorly characterized in terms of kidney survival, patient survival, and clinical characteristics. Therefore, we undertook a cross-sectional collaborative study to better characterize KIN-FAN1. Methods: To gather data, we distributed a REDCap survey on clinical characteristics and genetic variants of KIN-FAN1 to colleagues and case report authors. Results: Based on the survey, we identified 86 families affected (122 individuals) from 22 countries. There were 56 families (83 individuals) with a genetic diagnosis of KIN-FAN1, including 38 distinct FAN1 variants, and 30 families (39 individuals) with KIN with no predisposing risk factors and without molecular FAN1 testing. The median age at presentation was 38.5 years (interquartile range: 29-43), 62% male. Of the cohort, 46% had asymptomatic elevation of liver function tests, 39% had pulmonary complications, and 6% developed cancer. The median age of kidney failure was 45 years (95% confidence interval (CI): 38-56). Of the cohort, 27.1% died at a median age of 55 years (95% CI: 43-75). Pulmonary complications was/were the cause of death in 15.4% of patients on dialysis and 23.1% of kidney transplant recipients. Compared to other variants, patients with the p.W707X-FAN1 variant were at a significantly higher risk of pulmonary complications (adjusted odds ratio: 8.26 (95% CI: 1.7-40.1) and had a significantly shorter lifespan (hazard ratio: 3.24 (95% CI: 1.13-9.28). No genetic covariates were statistically associated with the progression to kidney failure. Conclusions: Patients with KIN-FAN1 develop kidney failure at a median age of 45 years. Survival is compromised with many dying of pulmonary disease.
SN - 0085-2538
SN - 1523-1755
ER -