# Genomic Approaches for Monogenic Kidney Diseases:
## 2 Genetic Testing: The Current Framework
### Targeted Panel Technology  
Targeted panel can assess multiple genes in parallel, saving time and reducing costs. Targeted panels focus on a selected set of genes with known or suspected associations with the disease under study. Employing panel technology is an effective approach to establishing a genetic diagnosis, in case of a clearly defined phenotype, to define the molecular diagnosis between phenocopies [52]. In the case of a defined phenotype and limited \begin{table}
\begin{tabular}{c l c c c c c c} \hline \hline \multirow{2}{*}{**CKD Clinical Presentation**} & \multirow{2}{*}{**Technologies**} & \multicolumn{2}{c}{**Pediatric**} & \multicolumn{2}{c}{**Pediatric/Adult**} & \multicolumn{2}{c}{**Adult**} \\  & & **N\({}^{\circ}\) Cases** & **Yield (\%)** & **N\({}^{\circ}\) Cases** & **Yield (\%)** & **N\({}^{\circ}\) Cases** & **Yield (\%)** \\ \hline \multirow{4}{*}{Specific} & Sanger [17; 18] & 35 & 14 & - & - & 2034 & 2 \\  & Targeted panel [19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30] & 31–1554 & 24–78 & 34–859 & 18–81 & 81–236 & 7–22 \\  & WES [31; 32; 33; 34] & 24–60 & 42–58 & - & - & 24–193 & 11–36.5 \\  & Mixed [35] & - & - & 45 & 64 & - & - \\  & WGS [36] & & & 144 & 70 & & \\ \hline \multirow{4}{*}{Non-specific} & Sanger & - & - & - & - & - & - \\  & Targeted panel [37; 38; 39; 40; 41; 42; 43; 44] & 188–832 & 28–40 & 50–1007 & 21–65 & 135–416 & 12–56 \\ \cline{1-1}  & WES [45; 46; 47; 48; 49; 50; 51; 52; 53; 54; 55; 56] & 104–1000 & 32.5–52 & 80–174 & 30–51 & 92–3315 & 9.3–34 \\ \cline{1-1}  & Mixed [57; 58; 59; 60; 61; 62; 63] & 158 & 51 & 74–309 & 31–57 & 231 & 42 \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Summary of included studies, grouped according to specific and non-specific chronic kidney disease (CKD) clinical presentations, age of the included cohort and reported technologies (Sanger; Targeted panel; WES—whole-exome sequencing; Mixed; WGS—whole-genome sequencing). Mixed considers results from targeted panel and WES. Figure 1: Boxplot for the distribution of diagnostic yield among the study included in the review. WES, whole-exome sequencing, WGS, whole-genome sequencing. genes to test, the approach is more simple than WES or WGS approaches. Furthermore, employing a specific genes panel helps prevent the discovery of incidental findings, as there is currently no consensus on how to report them. On the other hand, the targeted panel cannot be easily extended to include new genes. This means that the panel's content might quickly become outdated over time as new genetic associations are identified. Updating panels to include new genes associated with the disease or phenotype, requires a new design and validation of the modified panel [65]. Furthermore, in consideration of the multitude of clinical presentations, a significant number of different panels should be maintained by the analytical laboratory, thereby increasing the complexity and cost of this solution. Currently, targeted panels vary in the number of genes included in the analysis, with the largest panels able to analyze approximately 2000 genes. The clinical impact largely depends on the genes included and therefore, whether a differential diagnosis can be made. Table 1 reports diagnostic yields for targeted panels which are disease-specific, ranging from 6.8% for patients with renal stones [28] to 81% for patients with a clinical diagnosis of Autosomal Dominant Polycystic Kidney Disease (ADPKD) [26]. In the case of non-specific CKD clinical presentations, diagnostic yield from panels range from 28 to 40% for pediatric cases [37; 38], 21 to 65% for pediatric/adult cases [39; 40; 41] and 12 to 56% for adult cases. Most disease specific studies have used small panels (genes \(<\) 100), reporting an average yields of 36%. Only two targeted studies used a larger panel [20; 22], both on cystic populations, with an average yield of 75%.