A single-center study: three years of experience with whole-exome sequencing in diagnosing pediatric hematological disorders

Background Blood disorders in children can present with a wide range of nonspecific symptoms, which may overlap with other conditions. Traditional diagnostic methods can sometimes struggle to identify the underlying cause. Whole-exome sequencing (WES)—is increasingly recognized as a valuable diagnostic tool, as early genetic diagnosis can offer clarity, enabling more personalized treatment approaches and improving prognostic accuracy. Methods Between January 2022 and December 2024, 67 patients at the pediatric hematology department of Maternity and Children Hospital in Makkah, Saudi Arabia, underwent WES after conventional diagnostic methods failed to provide definitive diagnoses. We retrospectively analysed their results. Results The study included 67 patients with an average age of 6.5 ± 4.6 years (range 0.1–18 years), 53% of whom were male. The majority (88%) were of Saudi descent. WES provided a molecular diagnosis for 49% ( n = 33) of the patients, identifying pathogenic or likely pathogenic variants. In 11% ( n = 8) of the patients, no variants were found, whereas 38% ( n = 26) had variants of uncertain significance in phenotype-related genes. A nonhematological diagnosis was given to 28% of the patients. Conclusion Whole-exome sequencing is a valuable tool for diagnosing challenging pediatric blood disorders. The findings also underscore its importance in identifying complex or multifactorial disorders.