EP18.39: Novel pathogenic variant in thyroid hormone receptor interactor 11 gene associated with skeletal dysplasia

The thyroid hormone receptor interactor 11 (TRIP11) gene encodes a protein (GMAP-210) that is essential for the function of the Golgi apparatus. Null mutations in TRIP11 disrupt Golgi function, causing achondrogenesis type 1A (ACG1A). We presented a previously undefined mutation type of the TRIP 11 gene, which is also associated with skeletal dysplasia. Fetal anomaly screening evaluation revealed a female fetus with narrow thorax, severe limb shortening, craniosynostosis, flattened nasal bridge, decreased mineralization of lumbosacral vertebras, and diastematomyelia (see figure 1). Genetic analysis was performed using the next-generation sequencing method from the fetal sample obtained by amniocentesis. The variant was found in the TRIP11 gene as NM_004239.4:c.5153C>A(p.(Ser1718Ter)(Exon15) homozygous state (see figure 2). It was not found in databases (dbSNP, ClinVar, population databases). It was evaluated as ‘likely pathogenic’ according to the Varsome (PVS1-very strong-, PM2-supporting) and Franklin (Genoox) (PVS1-very strong-, PM2-moderate) platform (see figure 2). The parents decided to terminate the pregnancy (see figure 3). In conclusion, our findings revealed a variant in the TRIP11 gene with prenatal sonographic findings resembling ACG1A that has not been previously identified in databases. However, the postnatal consequences of this mutation could not be presented. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.