[P2-43] Three Patients with MED13L Haploinsufficiency Syndrome Associated with Variable Complications
[Introduction] MED13L haploinsufficiency syndrome is a clinical condition manifesting intellectual disability/developmental delay in association with variable complications including congenital heart defects and dysmorphic features. Most of the previously reported patients showed de novo loss-of-function mutations in MED13L. [Methodology] This study was performed in accordance with Helsinki declaration. After obtaining written informed consent, blood samples were accumulated from patients and their parents. Exome sequencing using TruSight One (Illumina) and exome hidden Markov model analysis were performed for patients with unknown etiologies. [Results] Additional cases of three patients with MED13L haploinsufficiency syndrome in association with variable complications were identified. One patient showed a de novo insertion (c.257delT) and T2-weighted high intensity in the occipital white matter. Sibling cases showed an intragenic deletion involving exons 3-14, which led to an in-frame deletion of MED13L. The deletion was inherited from their carrier mother who possessed a mosaic deletion. The elder sister of the siblings showed craniosynostosis. [Conclusions] This is the first cases of craniosynostosis and maternal mosaicism. Although craniosynostosis has never been reported previously, this may be a rare complication in patients with MED13L haploinsufficiency syndrome. Dysmorphic features were observed in the patients; however, most of the findings were non-specific. Further information would be required to understand this clinical condition better.