Omics tools in the diagnosis of ultra-orphan ultra-orphan diseases: MED13L haploinsufficiency syndrome

Abstract

Introduction: New generation technologies have allowed an advance in the diagnosis and approach of ultra-orphan genetic diseases, to offer greater possibilities in treatment and genetic counseling to families. MED13L syndrome affects the MED13L protein, which is important in early development of the heart, nerve cells in the brain, and structures of the face. Its variants can be the cause of developmental delay syndrome and facial dysmorphia with or without heart defects.

Case presentation: 4-year-old patient with history of generalized hypotonia, global neurodevelopmental delay, cognitive disability and dysmorphic features, given the clinical complexity a complete clinical exome sequencing was performed with analysis of mitochondrial DNA and copy number variation (CNV) with detection of alteration of the MED13L gene variant c.2965C>G (p.Pro989Ala), uncertain clinical significance, with subsequent implementation of new generation technologies and reclassification of significance to pathogenic variant through bioinformatic analysis, which allowed reaching the a specific origin of the pathology.

Conclusions: The importance of the use of new generation technologies and bioinformatic tools in the specific diagnosis of complex diseases is highlighted. New technologies act as a tool to help establish a targeted protocol, genetic counseling and thus assess the risk of heritability, prognosis, and therapeutic perspectives of ultra-orphan diseases.