Abstract
Growth disorders resulting in extreme short stature (ESS) are often a result of deficiency in growth hormone (GH) released from the pituitary gland or a defective GH releasing receptor. Genetic defects in the GH1 and GHRHR genes account for around 11.1-20% of ESS cases, resulting in a rare condition called isolated GH deficiency (IGHD). We describe the characterization of a GH1 genetic defect discovered in a 3-year-old male patient with ESS, developmental failure and undetectable serum levels of GH. There was a family history of short stature, with both parents being short. Whole genome sequencing of the patient DNA revealed a large, novel 6 kb homozygous deletion spanning the entire GH1 gene in the patient. While the deletion was homozygous in the proband, it was present in the heterozygous state in the parents. Thus, we report a novel homozygous deletion including the GH1 gene leading to IGHD-type 1A associated with ESS.