The Role of Next Generation Sequencing in Diagnosis of Patients with Rare Syndromic Short Stature

Abstract

Objective: To examine the genetic causes of short stature, algorithms are applied to make the diagnosis in a stepwise manner by applying different genetic technique options at different stages of diagnosis, depending on the evaluation of the clinicians. In this study, we aimed to evaluate genetic diagnosis in Turkish patients with short stature of unknown etiology using next negeration sequencing (NGS).

Methods: In cases with an unknown etiology of short stature, NGS was applied. For this aim, 19 cases from 17 families were included. The clinically relevant variants detected in the cases were confirmed by the Sanger method.

Results: For 11 of 19 patients (57.9%) with short stature, a genetic diagnosis was obtained by NGS. In 11 patients, 9 different genetic variants were identified. We detected 4 novel variants (LTBP3: c.2919C>G, TRPS1: c.2894G>T, CNOT1: c.4967dup, ANKRD11: c.5273C>T). These novel variants were associated with Dental Anomalies and Short Stature syndrome (DASS), Trichorhinophalangeal syndrome (TRPS), Vissers-Bodmer syndrome (VIBOS) and KBG syndrome (KGBS).

Conclusion: These results show that NGS significantly increases the diagnostic yield of patients with short stature. NGS provides great benefits for both patients and clinicians in clinical use, and also enables the detection of novel rare variants.