ESPE Abstracts

Objectives: Owing to the tremendous advances in next-generation sequencing technology, numerous monogenic causes of growth disorders have been identified. Identifying novel rare genetic causes of short stature (SS) is quite challenging. In 2017, we reported a mutation analysis of 15 patients with undiagnosed syndromic SS or overgrowth. In this study, 6 mutations in another 10 Korean patients with unexplained syndromic SS are reported. The aim of this study is to identify underlying genetic causes of unexplained SS.

Methods: Ten pediatric patients with profound SS, mean height of −2.5 SD score (SDS), and a normal growth velocity, some of whom had additional dysmorphic features, were subjected to targeted exome sequencing (TES) study using the Next Seq platform and a TruSight One panel.

Results: Among the 10 patients with unexplained SS, 6 different disorders were identified, and the diagnostic yield was 60%. In the patients with SS, Coffin-Lowry syndrome (CLS) with a novel missense mutation inherited from mother, Cleidocranial dysplasia, Acid-bile subunit deficiency (ALSD) with a novel compound heterozygous mutation, Coffin-Siris syndrome (CSS) with a novel nonsense mutation, X-linked creatine transporter deficiency with speech delay, and Acromesomelic dysplasia, Maroteaux type (AMDM) were identified.

Conclusions: TES led to the diagnosis of a monogenic disorder in six of the 10 individuals, including cases with three novel mutations. This study shows that TES is a very promising tool for the identification of pathogenic mutations in patients with unexplained syndromic short stature.