Background: Cystic kidney disease (CyKD) is a heterogeneous group of disorders in which clusters of cysts develop in the kidneys. Although most childhood CyKD is caused by genetic derangement, they are diagnosed through clinical manifestations and imaging studies. Despite the heterogeneity of inherited CyKD, the majority of affected individuals share common clinical features, making a definite diagnosis and genetic counseling difficult. Historically, molecular diagnosis of CyKD was performed by expensive and laborious Sanger sequencing of potential mutated genes. The newer next-generation sequencing (NGS) offers rapid and cost-effective parallel sequencing of large panels of genes or the whole exome. NGS has been reported to change clinical-based diagnoses in 20-40% of childhood CyKD cases. Objective: To identify the disease-causing mutations in children with CyKD using whole-exome sequencing (WES). Design/Methods: The study was approved by the Human Research Ethics Committee at Ramathibodi Hospital, Mahidol University (COA no. MURA 2023/439). Patients aged ≤ 18 years with at least one kidney cyst were included. Exclusion criteria was the presence of advanced chronic kidney disease due to other apparent causes. After obtaining informed consent, we collected and reviewed demographic data, pedigrees, family histories, clinical features, imaging study results, and clinical diagnoses. Blood samples were collected, followed by DNA extraction and WES. Sequence reads will then be mapped to the human reference genome assembly for variant calling in known or potential CyKD genes. Detected variants will be analyzed and filtered using available human genome browsers. Variants with the most potentially deleterious effects will remain. Subsequently, Sanger sequencing was performed to confirm the mutation and assess intrafamilial segregation using the original DNA samples from the patients and their parents. Currently, 83 blood samples (33 families) have been obtained and are in the process of sequencing. The descriptive analysis of disease-causing mutations will be completed in February 2024.
.jpg "Praewa Sophark, MD (she/her/hers) photo")