SAT-198 Identification of Genetic Causes in Pediatric Growth Hormone Deficiency by Whole Exome Sequencing

Abstract Disclosure: H. Jo: None. Y. Cho: None. Background: Growth hormone deficiency (GHD) is a disorder of growth hormone secretion. In patients with faltering growth and/or a suboptimal response to treatment with recombinant human growth hormone, additional phenotypes, such as severe short stature and body disproportion, should be checked, and additional diagnoses considered. This study therefore aimed to analyze the genetic causes of short stature by performing next-generation whole-exome sequencing (WES) in children diagnosed with GHD and short stature who were recommended for genetic testing.Methods: Twenty children diagnosed with GHD who met the guidelines for recommending genetic testing were selected and underwent WES.Results: Of the 20 patients analyzed, genetic causes of short stature were identified in two. The molecular diagnoses were idiopathic familial short stature caused by deletion of the SHOX gene and Zhu-Tokita-Takenouchi-Kim syndrome caused by a heterozygous mutation in the SON gene. In other patients, a single candidate variant (compound heterozygous mutation in DPH1) was discovered. Although none of these genes were previously known to cause GHD, our results indicate that they can cause short stature.Conclusions: As WES is used to investigate the pathogenesis of short stature and GHD, many related genes are being discovered, which will make genetic counseling possible for future generations. Although the diagnostic rate remains low, WES is a useful testing method. As such, patients should be screened and tested as necessary. We anticipate that the accumulation of data from studies such as ours will lead to changes in the guidelines for the diagnosis and treatment of patients with GHD. Presentation: Saturday, July 12, 2025