Severe Growth Hormone Deficiency in an Indian Boy Caused By a Novel 6 kb Homozygous Deletion Spanning the GH1 Gene

Growth disorders resulting in extreme short stature are often a result of deficiency in growth hormone released from the pituitary gland or defective growth hormone releasing receptor. Genetic defects in the GH1 and GHRHR genes account for around 11.1-20% of extreme short stature cases, resulting in a rare condition called Isolated Growth Hormone Deficiency. We describe the characterization of a GH1 genetic defect discovered in a 3-year-old male patient with extreme short stature, developmental failure and undetectable serum levels of growth hormone. There is a familial 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 subjects, it was found in a heterozygous state in the parents. Thus we report a novel homozygous deletion including the GH1 gene leading to Isolated Growth Hormone Deficiency- Type 1A associated with extreme short stature.