Ethnically unique disease burden and limitations of current expanded carrier screening panels

The purpose of the study is to identify the recessive diseases currently affecting real-world pediatric patients in Taiwan, and whether current extended carrier screening panels have the coverage and detective power to identify the pathogenic variants in the carrier parents.

A total of 132 trio-samples were collected from May 2017 to March 2022. The participants were parents of pediatric intensive care unit patients who were critically ill or infants with abnormal newborn screening results. A retrospective carrier screening scheme was applied to analyze only the carrier status of pathogenic or likely pathogenic recessive variants resulting in diseases in their children. The recessive disorders diagnosed in our cohort were compared with the gene content in commercial panels.

Mutations in COQ4, PEX1, OTC, and IKBKG were the most frequently identified. In the parents of 44 children with confirmed diagnoses of recessive diseases, 47 (53.40%) screened positive for being the carriers of the same recessive disorders diagnosed in their children. The commercial panels covered 35.13% to 54.05% of the disorders diagnosed in this cohort.

Clinicians and genetic counselors should be aware of the limitations of current extended carrier screening and interpret negative screening results with caution. Future panels should also consider genes with ethnically unique mutations such as pathogenic variants of the COQ4 gene in the East Asian population.