[Expanded carrier screening for 216 diseases in a cohort of 3 097 healthy Chinese individuals of childbearing age].

<b>Objective:</b> To determine the carrier frequency and hot-spot variants of a custom-designed expanded carrier screening (ECS) panel with 216 diseases (216-ECS panel) within a Chinese population of childbearing age. <b>Methods:</b> Whole-exome sequencing data from a cohort of 3 097 unrelated healthy individuals (including 1 424 couples) from Peking Union Medical College Hospital between January 2013 and December 2023 were analyzed. Totally 220 genes which inherited in a recessive manner of 216-ECS panel were included in the analysis. The analysis included variant carrier rate, gene carrier rate, cumulative carrier rate, at-risk couple rates, and variant spectrum. <b>Results:</b> (1) Pathogenic variants were identified in 1 472 (47.53%, 1 472/3 097) individuals, with an average of 0.65 pathogenic variants per individual. The rate of at-risk couples was 3.93% (56/1 424). (2) A total of 180 genes were identified, with 16 genes exhibiting a gene carrier rate of ≥1% and 33 genes having a rate of ≥0.5%, most of which were associated with inherited metabolic diseases. Noteworthy genes with higher gene carrier rates and high-frequency variants included <i>GJB2</i>: c.235del, <i>PAH</i>: c.728G>A, <i>ATP7B</i>: c.2333G>T, <i>SLC26A4</i>: c.919-2A>G, <i>GALC</i>: c.1901T>C, <i>POLG</i>: c.2890C>T, <i>SLC22A5</i>: c.1472C>G, <i>USH2A</i>: c.2802T>G, <i>SLC25A13</i>: c.852_855del, <i>GAA</i>: c.761C>T and c.752C>T. <b>Conclusion:</b> This study offers a focused analysis of carrier frequencies and hot-spot variants of 216 diseases of the ECS panel constructed by our laboratory among the Chinese population, laying a foundation for the development of ECS programs tailored to the Chinese population.