Kidney Week

Abstract: FR-PO675

Rare Diseases: Significance of Molecular Genetic Analyses in Finding a Diagnosis

Session Information

• Genetic Kidney Diseases: Cohort Studies - Genetic Associations and Diagnoses
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Wagner, Annette D., Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Annette D. Wagner, MD

• Hoffer, Sena, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Sena Hoffer, MD

• Beger, Christian, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Christian Beger, MD

• Kempf, Christian, Center for Human Genetics, Tübingen, Baden-Württemberg, Germany

Christian Kempf, MD

• Kreuz, Friedmar Raimund, Center for Human Genetics, Tübingen, Baden-Württemberg, Germany

Friedmar Raimund Kreuz, MD

• Biskup, Saskia, Center for Human Genetics, Tübingen, Baden-Württemberg, Germany

Saskia Biskup

• Gabriel, Heinz, Center for Human Genetics, Tübingen, Baden-Württemberg, Germany

Heinz Gabriel, PhD

Background

Diagnosing rare diseases remains a challenge despite improved diagnostic methods. In the past, it often took patients years to receive a final diagnosis. We aim to show that genetic testing should be used as one of the first steps in the diagnostic process of patients with rare diseases. Whereas in the past only single-gene diagnostics were available, today a large number of genes can be sequenced in parallel using next-generation sequencing.

Methods

In the outpatient clinic for rare inflammatory diseases 85 patients with unclear diagnoses have undergone molecular genetic analyses over the last years. Most diagnoses could be made by whole exome sequencing (WES). This involves sequencing of the coding regions of all human genes. Using bioinformatic methods, the genes that can be associated with the symptoms are "filtered out" from the data set. This has the great advantage that the selection of genes can be kept up-to-date and flexible.

Results

In the case of atypical courses or non-response to treatment, genetic tests were arranged, which led to the correct diagnosis in a total of 85 patients. In addition to a larger group of 25 patients with periodic fever syndromes, neurological disorders could be identified in 14 patients. Among this group 8 patients were diagnosed with tuberous sclerosis. 12 Patients were affected by a disorder of the skeletal system (mostly hypophosphatasia). In 7 patients a muscle disease was found. The other patients were classified as follows: kidney disease (6x), hereditary cancer syndromes (6x), immunological disorder (5x), metabolic disorder (2x), hepatic disorder (1x), ophthalmological disorder (1x), heart defect (1x), connective tissue disorder (1x) and 3 patients with other conditions.

Conclusion

The recent changes in the field of genetics have an impact on our work in outpatient clinics for rare diseases. The diagnostic direction from "phenotype to genotype" has therefore often been reversed to "genotype to phenotype". Frequently, several single-gene analyses were carried out in succession until the causative pathogenic variant could be identified. In our clinic, diagnoses could mostly be made by WES. Thanks to the close co-operation between our outpatient clinic and a genetic diagnostics laboratory, a final diagnosis can be made in many cases within a few weeks.

Funding

• Private Foundation Support