Application of Genomics for the Precision Molecular Diagnosis of Rare Short Stature Disorders

Abstract

Idiopathic and extreme short stature are defined respectively as heights with unknown causes below -2SDs and heights below -3SDs for an individuals’ age, gender and ethnicity. Most of the patients are suspected to have highly penetrant, monogenic mutations contributing to their phenotype. There are over 600 known genetic conditions that result in short stature, many are rare disorders with multiple comorbidities. Recombinant human growth hormone (rhGH) is the standard treatment for patients with growth hormone deficiency and has been shown to be effective with some other short stature disorders. However, for some rare genetic short stature disorders, rhGH treatment is contraindicated. Unfortunately, due to a lack of precise diagnosis, most patients undergo the same treatment, even though their etiology may differ. Furthermore, there is a failure to monitor for the development of other potential complications due to a lack of understanding of exact risks each patient faces. This project aims to contribute knowledge that could have an impact on the current method of diagnosis, treatment and monitoring of patient health. By conducting whole genome sequencing and analysis of patient and their families’ DNA, we attempted to understand the molecular and genetic basis of their disease. We discovered novel, rare variants within this unique population that could help further our insight into genetic short stature causes and especially growth hormone deficiency. This project exemplifies the application of genomics and precision medicine for diagnosis of short stature disorders in Qatar.

Date of Award	2021
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences