Comparative profiles of pediatric Mendeliome: A Single-Centre 572-Whole-Exome Sequencing Study in Xinjiang.

OBJECTIVE To compare the diagnostic yields and utility of whole-exome sequencing (WES) for Mendelian disorders in pediatric patients of different ethnic backgrounds in Xinjiang.

METHODS A retrospective analysis of 572 pediatric patients suspected of Mendelian disorders, admitted to the Pediatric Center of the First Affiliated Hospital of Xinjiang Medical University from January 2016 to June 2020. WES was performed in accredited laboratories, and reports were verified by supervising physicians.

RESULTS The overall positive diagnostic yield was 42.3%. Uyghur children had higher yields (46.5%) than Han children (36.2%), and patients from consanguineous families (70%) had higher yields than those from non-consanguineous families (40.8%). Recessive diseases were more common in Uyghur patients (60.8%) than in Han patients (29.8%). Most variants in consanguineous families were homozygous (60%), with significant fractions of de novo (27.3%) and compound heterozygous variants. Four patients had dual molecular diagnoses, and 21 novel clinical phenotypes were reported. Medication and clinical management were altered for 61.0% and 89.2% of the patients with positive findings, respectively.

CONCLUSION Exome testing shows higher diagnostic yield and clinical utility, especially for patients from consanguineous families in Xinjiang. Carrier screening could effectively prevent severe genetic disorders in the region, expanding the genomotype and phenomotype in the Chinese pediatric population.