1. Figure 1 The genomic nephrology workflow: genetic diagnosis and clinical application
Figure 1 |The genomic nephrology workflow: genetic diagnosis and clinical application. The first step in obtaining a genetic diagnosis for a patient with kidney disease is to characterize their disease phenotype by summarizing their clinical history and other relevant data (for example, findings from biochemical, imaging, and histopathological studies). This phenotype is then used to guide the choice of genetic testing modality. Among patients with genetically heterogeneous disease aetiologies, clinically ambiguous phenotypes, or null results obtained using targeted forms of genetic testing such as Sanger sequencing or targeted next-generation sequencing (NGS) panels, increasingly broad sequencing approaches can be applied, including Mendeliome panels, which can detect variants in all known disease-causing genes; whole-exome sequencing (WES), which can detect variants in all coding regions; and whole-genome sequencing (WGS), which can detect variants in all coding and non-coding regions. Clinical sequence interpretation should be performed according to consensus guidelines66,67,182. This process involves identifying genes that are relevant to the phenotype of the patient, prioritizing variants on the basis of prior reports in disease cases as well as compatibility with the prevalence and genetic pathogenesis of the associated disease, and assessing the concordance between the genetic findings and the clinical phenotype. If deemed diagnostic, these primary findings, together with secondary findings if the patient has opted to receive them, can be returned and used to inform prognosis and guide personalized care, including targeted work‑up and surveillance, choice of therapy, referral for clinical trials and family counselling.
Groopman, E. E. et al. (2018) Genomic medicine for kidney disease
Nat. Rev. Nephrol. doi: /nrneph