Kidney Week

Abstract: TH-PO657

Development of Strategies for Genetic Diagnosis of Hereditary Glomerulopathies, Tubulopathies, and Cystic Kidney Diseases by the Sequencing Sets of Genes

Session Information

• ADPKD: Genetic and Model Studies
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

• 1001 Genetic Diseases of the Kidney: Cystic

Authors

• Besada-Cerecedo, M. Lara, IDIS, Santiago de Compostela, Spain

M. Lara Besada-Cerecedo,

• Carrera cachaza, Noa, Fundación Instituto de Investigación Sanitaria de Santiago (FIDIS), Santiago de Compostela, Spain

Noa Carrera cachaza,

• Garcia-Murias, Maria, Fundación Instituto de Investigación Sanitaria de Santiago (FIDIS), Santiago de Compostela, Spain

Maria Garcia-Murias,

• Barcia de la Iglesia, Ana, IDIS, Santiago de Compostela, Spain

Ana Barcia de la Iglesia,

• Amigo, Jorge, University of Santiago de Compostela, Santiago de Compostela, Spain

Jorge Amigo,

• Sobrino, Beatriz, University of Santiago de Compostela, Santiago de Compostela, Spain

Beatriz Sobrino,

• Carracedo, Angel, University of Santiago de Compostela, Santiago de Compostela, Spain

Angel Carracedo,

• Diaz-Rodriguez, Candido, University Clinical Hospital of Santiago de Compostela (CHUS), Santiago de Compostela, Spain

Candido Diaz-Rodriguez,

• Garcia-Gonzalez, Miguel A., Health Research Institute of Santiago de Compostela (IDIS)., Santiago de Compostela, GAL, Spain

Miguel A. Garcia-Gonzalez,

Background

Accurate clinical diagnosis in hereditary renal pathologies, especially glomerular and tubular disease, has proven to be difficult, as different pathologies may appear as clinical phenocopies. Genetic studies have the advantage of ensuring an accurate diagnosis and anticipate the disease. The implementation of NGS technology into routine genetic diagnostic practices allows the screening of large sets of genes in a single test.

Methods

Our group, based on the clinical classification, generated different panels for the sequence of renal disease genes in single tests: (1) panel for cystic kidney disease (up to 72 genes) (2) panel for glomerular disease (26 genes) and (3) panel for tubular disease (36 genes). Also, our group solved one of the limitations of conventional pre-designed NGS kits for target enrichment in regions with high homology pseudogenes (such as the PKD1 gene) by developing particular primers to amplify specifically the replicated region of PKD1 gene (exons 1-34).

Results

By analyzing a cohort of 291 families with PKD clinical diagnosis, we identified the causal mutation in 88% (n=255) of the families. In 94% (n=240) of these cases the clinical and genetic diagnosis were concordant. Of the 71 patients with a clinical diagnosis of glomerular disease and 31 with tubular disease subjected to genetic analysis, we identified the causal mutation in 62% (n=44) and 52% (n=16) of the cases, respectively. The concordance between genetic and clinical diagnosis was 66% (n=29) for the glomerular cohort and 69% (n=11) for tubular cohort. Most cases of misdiagnosis were associated with syndromic diseases with very similar phenotypes, such as Gitelman and Bartter syndromes.

Conclusion

The strategy of grouping genes by phenotype for genetic testing probed to be efficient in finding the causal mutation. Our results make clear the need of a genetic test to avoid misdiagnosis of certain renal pathologies.