Diagnostic yield and genetic landscape of rare pediatric diseases in Vietnam identified by exome sequencing.

Childhood diseases, especially those involving genetic factors, sometimes present challenges in clinical confirmation due to their nonspecific manifestations and multisystem involvement. Understanding genetic etiology, the prevalence of these diseases, and establishing an appropriate genetic approach were key to timely intervention and effective disease management, particularly in low-resource countries. In Vietnam, a lack of data has been reported regarding the diagnostic yield and variant spectrum of rare and complicated diseases in pediatric patients. A retrospective study was conducted on nationwide pediatric patients presenting clinical abnormalities suspected of genetic causes, whose genetic data should be available. Data was extracted from medical reports and statistically summarized. About 369/958 (38.52%) probands were diagnosed with related genetic diseases; of them, 35.3% had single-gene disorders, and 5.1% had copy number variants. Over 70% of participants were 5 years old or younger (mean age of 3.13 ± 4.24 years). Copy number variant sequencing (CNV-seq) revealed 56 copy number variants (75.0% micro-deletions, 21% micro-duplications). Whole-exome sequencing (WES) as well as a 4503-gene panel detected 448 variants (90% of autosomal variants). In 338 single-gene cases, related phenotypes mainly affected the neurological system (31.1%). Using advanced genetic testing in a local setting, as WES and a 4503-gene panel integrated CNV-seq, could help achieve diagnostic yields comparable to established international programs. This study offers a preliminary approach to clinical diagnosis strategies and therapeutic awareness for genetic disorders in childhood illnesses in Vietnam.