ESPE Abstracts

Background: Genetics plays a strong role in height. However, for most patients, no cause for the short stature can identified. Whole-exome sequencing (WES) is becoming an increasingly important tool for detecting novel genetic causes of short stature. Blood is the preferred DNA source for germline studies using WES. However, DNA from saliva is a more convenient and cost-effective alternative.

Objectives: We aim to identify known and novel genetic causes of short stature.

Methods: We recruited 12 children with short stature of unknown etiology. We conducted WES of the patients and their family members. Saliva samples were collected from 12 subjects with syndromic short stature. A series of DNA isolation optimization experiments were performed on the saliva samples. WES was performed on samples from optimized saliva DNA isolation and subsequent Sanger sequencing was conducted on isolated DNA from blood for the validation in trio. The average coverage for WES was 100X. We used an analysis pipeline to identify rare nonsynonymous genetic variants that cause the short stature.

Results: We identified a genetic cause of short stature in 11 of the 12 patients. This included cases of CDK13-related disorder, Braraitserwinter syndrome 1, Rubinstein-Taybi 2, COHEN syndrome, Pierpont syndrome, Trichorhinophalangeal syndrome, SRMMD(Short Stature, Rhizomelic, with Microcephaly, Micrognathia, and Developmental delay), VERHEIJ syndrome, and Arthrogryposis, distal type2B (Sheldon-Hall syndrome), as well as two cases of the ZTTK syndrome.

Conclusions: This analysis represents, to our knowledge, the first comprehensive examination of WES data generated from saliva in Korea. Saliva might be a good alternative DNA source for WES to identify genetic causes of short stature. This indicates that high quality sequencing data can be derived from saliva samples for germline genetic analyses.