Next-generation sequencing-based mutational analysis of idiopathic short stature and isolated growth hormone deficiency in Korean pediatric patients

We investigated the distribution of short stature-associated mutations in Korean pediatric patients with idiopathic short stature (ISS) and isolated growth hormone deficiency (IGHD) via targeted next-generation sequencing (TNGS). We employed a 96-gene TNGS panel for short stature in a total of 144 patients (5-19 years-old) previously diagnosed with ISS or IGHD and identified heterozygous pathogenic or likely pathogenic genetic variants in 14 (10%) patients. Of the mutated genes, PROKR2 (n = 3) is associated with gonadotropin-releasing hormone deficiency or hypopituitarism, while FGFR1 (n = 1) and NPR2 (n = 3) encode growth plate paracrine factors. FBN1 (n = 1), COL9A1 (n = 1), MATN3 (n = 1), and ACAN (n = 3) regulate the cartilage extracellular matrix, while PTPN11 (n = 1) controls intracellular pathways. Six patients had IGHD, and eight patients had ISS. The current findings highlight the utility of TNGS for determining the genetic etiology in these patients.