Comprehensive review on growth hormone (GH) mutations and sequence variants in children with growth hormone deficiency

Growth hormone (GH) is a vital peptide hormone res­pon­sible for regulating growth, development and numerous me­­ta­­bo­lic functions in humans and other vertebrates. Com­pri­sing 190 amino acids, GH is synthesized and secreted by the somatotroph cells located in the anterior pituitary gland. Its gene, GH1, is part of a cluster of five related genes span­ning approximately 50 kilobases on chromosome 17q22-24. The GH1 gene itself is about 2 kilobases in length and consists of five exons and four introns. Growth hor­mone exerts its effects both directly and indirectly through insulin-like growth factor-1 (IGF-1), influencing a broad spectrum of physiological processes. Primarily, GH is essential for somatic growth, significantly contributing to the regulation of height and skeletal development du­ring childhood and adolescence. In adults, it continues to play a role in maintaining body composition, muscle and bone mass, and metabolism. Beyond growth, GH also af­fects reproductive function, cellular regeneration, and im­mu­ne system modulation, underscoring its multifaceted im­por­tance in human physiology. Dysregulation of growth hor­mone secretion can result in various disorders, such as gi­gan­tism or acromegaly in cases of excess, and growth hor­mone deficiency (GHD) leading to stunted growth and me­ta­bolic issues. Understanding the molecular structure, ge­ne­tic regulation and physiological functions of growth hor­mone is crucial for the diagnosis and treatment of such con­di­tions. This review aims to provide an overview of growth hormone’s biological and genetic profile, as well as its significant roles in human development and health.