Customized
15 affiliations
- 1Clinical Area of Nephrology and Immunology, Health in Code, A Coruña, Spain
- 2Genetic Diagnostic Department, Health in Code, A Coruña, Spain
- 3Research and Development Department, Health in Code, Valencia, Spain
- 4Department of Nephrology, Clínica Universitaria de Navarra. Pamplona, Spain
- 5Department of Nephrology, University Hospital La Paz, Madrid, Spain
- 6Clinical Genetics Unit, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain
- 7Department of Nephrology, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain
- 8Department of Nephrology, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain; School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
- 9Department of Nephrology, University Hospital Marqués de Valdecilla-IDIVAL, Santander, Spain
- 10Department of Nephrology, University Hospital of A Coruña, A Coruña, Spain
- 11Molecular Genetics Laboratory, Fundació Puigvert, Institut de Recerca Sant Pau (IR-Sant Pau), Barcelona, Spain, ERKNet Reference Center, RICORS2040renal
- 12Department of Nephrology, University Hospital Virgen de la Victoria. Málaga, Spain
- 13Department of Nephrology and Kidney Transplant, National Reference Center for Complex Glomerular Diseases (CSUR), Fundació de Recerca Clínic Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic Barcelona, Barcelona University, Barcelona, Spain
- 14Department of Nephrology, University Hospital Infanta Leonor, Madrid, Spain
- 15Department of Nephrology, University Hospital Infanta Leonor, Madrid, Spain; University Autónoma de Madrid, Madrid, Spain, and University Complutense de Madrid, Madrid, Spain
Abstract
Introduction: Inherited kidney disease (IKD) is the second most common cause of prevalent kidney failure on kidney replacement therapy in Europe. However, it remains underdiagnosed, in part, because of suboptimal genetic test resolution. The genetic diagnosis of autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by MUC1 gene variants (ADTKD- MUC1 ) is technically challenging. Methods: We implemented a customized library for short-read high-throughput sequencing (SR-HTS) with specific bioinformatic approaches to enhance the genetic diagnosis of ADTKD- MUC1 . Specific analysis of the variable number tandem repeat (VNTR)- MUC1 region was performed in 550 patients with suspected IKD lacking an identifiable genetic cause using customized SR-HTS. We used a combination of techniques to confirm the genetic variant detected by SR-HTS. Results: Overall, 28 patients (5% [25/550]) had ADTKD- MUC1 with DupC (almost 90% [25/28] of MUC1 variants) or DupA (10%) MUC1 pathogenic frameshift variants. More than half of these cases required specialized bioinformatics analysis to detect the variants. These variants were validated using Sanger, SNaPshot, or long-read sequencing (LRS) according to the location and mutation type. Conclusion: This study presents an applicable solution of a customized SR-HTS approach for the systematic screening of MUC1 gene variants, with particular emphasis on the detection of frameshift alterations within the VNTR region that generate pathogenic MUC1 neoproteins associated with ADTKD- MUC1 . Integrating this strategy into routine diagnostic workflows increased the overall diagnostic yield while reducing the technical complexity associated with the sequential application of multiple methodologies.
BibTeX
@article{garciaaznar2026customized,
title = {{Customized}},
author = {José María García-Aznar and María Lara Besada-Cerecedo and Nerea López Aguirre and Jorge Pérez Álvarez and Mireia Boluda-Navarro and Sonia González Alvaredo and Iván Lesende and Laura Castañeda-Infante and Lina León-Machado and Alfredo Santana Rodríguez and Vanessa Pérez-Gómez and Elena Gomá Garces and Alberto Ortiz and Gema Fernández Fresnedo and Mercedes Cao Vilarino and Elisabet Ars Criach and Jose Carlos Prado de la Sierra and Rosa María Escaño Marín and Mónica Martín Velázquez and Miquel Blasco and Fabio L. Procaccini and Patricia de Sequera},
journal = {Kidney International Reports},
year = {2026},
month = sep,
doi = {10.1016/j.ekir.2026.107095},
url = {https://doi.org/10.1016/j.ekir.2026.107095},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Customized
AU - José María García-Aznar
AU - María Lara Besada-Cerecedo
AU - Nerea López Aguirre
AU - Jorge Pérez Álvarez
AU - Mireia Boluda-Navarro
AU - Sonia González Alvaredo
AU - Iván Lesende
AU - Laura Castañeda-Infante
AU - Lina León-Machado
AU - Alfredo Santana Rodríguez
AU - Vanessa Pérez-Gómez
AU - Elena Gomá Garces
AU - Alberto Ortiz
AU - Gema Fernández Fresnedo
AU - Mercedes Cao Vilarino
AU - Elisabet Ars Criach
AU - Jose Carlos Prado de la Sierra
AU - Rosa María Escaño Marín
AU - Mónica Martín Velázquez
AU - Miquel Blasco
AU - Fabio L. Procaccini
AU - Patricia de Sequera
PY - 2026
DA - 2026/09/25
JO - Kidney International Reports
DO - 10.1016/j.ekir.2026.107095
UR - https://doi.org/10.1016/j.ekir.2026.107095
AB - Introduction: Inherited kidney disease (IKD) is the second most common cause of prevalent kidney failure on kidney replacement therapy in Europe. However, it remains underdiagnosed, in part, because of suboptimal genetic test resolution. The genetic diagnosis of autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by MUC1 gene variants (ADTKD- MUC1 ) is technically challenging. Methods: We implemented a customized library for short-read high-throughput sequencing (SR-HTS) with specific bioinformatic approaches to enhance the genetic diagnosis of ADTKD- MUC1 . Specific analysis of the variable number tandem repeat (VNTR)- MUC1 region was performed in 550 patients with suspected IKD lacking an identifiable genetic cause using customized SR-HTS. We used a combination of techniques to confirm the genetic variant detected by SR-HTS. Results: Overall, 28 patients (5% [25/550]) had ADTKD- MUC1 with DupC (almost 90% [25/28] of MUC1 variants) or DupA (10%) MUC1 pathogenic frameshift variants. More than half of these cases required specialized bioinformatics analysis to detect the variants. These variants were validated using Sanger, SNaPshot, or long-read sequencing (LRS) according to the location and mutation type. Conclusion: This study presents an applicable solution of a customized SR-HTS approach for the systematic screening of MUC1 gene variants, with particular emphasis on the detection of frameshift alterations within the VNTR region that generate pathogenic MUC1 neoproteins associated with ADTKD- MUC1 . Integrating this strategy into routine diagnostic workflows increased the overall diagnostic yield while reducing the technical complexity associated with the sequential application of multiple methodologies.
SN - 2468-0249
ER -