Opitz GBBB syndrome with total anomalous pulmonary venous connection: A new MID1 gene variant

Abstract

BackgroundOpitz GBBB syndrome (GBBB) is an X‐linked disease characterized by midline defects, including congenital heart defects. We present our diagnostic approach to the identification of GBBB in a consanguineous family in which two males siblings were concordant for a total anomalous connection of pulmonary veins and minor facial dysmorphias.MethodsTargeted exome sequencing analysis of a 380‐gene panel associated with cardiovascular disease was performed on the propositus. Interpretative analysis of the exome results was conducted, and 3D models of the protein changes were generated.ResultsWe identified a NM_000381.4:c.608G>A;p.(Arg203Gln) change in MID1, affecting the conformation of the B‐box 2 domain of the protein, with a zinc finger structure and associated protein interactions. This clinical phenotype is consistent with GBBB; however, the type of congenital heart disease observed in this case has not been previously reported.ConclusionA new likely pathogenic variant on MID1 c.608G>A was found to be associated with Opitz GBBB syndrome.