Proband-only medical exome sequencing as a cost-effective first-tier genetic diagnostic test for patients without prior molecular tests and clinical diagnosis in a developing country: the China experience

Purpose To evaluate the performance of proband-only medical exome sequencing (POMES) as a cost-effective first-tier diagnostic test for pediatric patients with unselected conditions. Methods A total of 1,323 patients were tested by POMES, which targeted 2,742 known disease-causing genes. Clinical relevant variants were Sanger-confirmed in probands and parents. We assessed the diagnostic validity and clinical utility of POMES by means of a survey questionnaire. Results POMES, ordered by 136 physicians, identified 512 pathogenic or likely pathogenic variants associated with over 200 conditions. The overall diagnostic rate was 28.8%, ranging from 10% in neonatal intensive care unit patients to over 35% in pediatric intensive care unit patients. The test results had an impact on the management of the 45.1% of patients for whom there were positive findings. The average turnaround time was 57 days; the cost was $360/case. Conclusion We adopted a relatively efficient and cost-effective approach in China for the molecular diagnosis of pediatric patients with suspected genetic conditions. While training for clinical geneticists and other specialists is lagging behind in China POMES is serving as a diagnostic equalizer for patients who do not normally receive extensive clinical evaluation and clinical diagnosis prior to testing. This Chinese experience should be applicable to other developing countries that are lacking clinical, financial, and personnel resources.