A New Family with a Novel OTUD6B Mutation: Practicing Whole Exome Sequencing for Antenatal Diagnosis of Tetralogy of Fallot

OTUD6B, which encodes a member of the ovarian tumor domain-containing deubiquitinating enzyme, has recently been associated with autosomal recessive intellectual disability syndrome with seizures and dysmorphic features. Here, we report one additional case with Tetralogy of Fallot (ToF), who has microcephaly and dysmorphic features along with renal parenchymal disease with simple cortical cysts. The family's first pregnancy was medically terminated due to antenatal diagnosis of ToF. A novel homozygous variant in OTUD6B (c.815T>G; p.[Ile272Arg]) was revealed by whole exome sequencing (WES) along with a previously reported heterozygous PKD1 variant, unraveling the blended phenotype observed in the proband. Our findings highlight the importance of WES for the prenatal diagnosis of ToF and expand the OTUD6B mutational spectrum.

Automated summary

OTUD6B gene mutations can cause a syndrome with intellectual disability, seizures, and dysmorphic features. This study reports a case with Tetralogy of Fallot (ToF), along with microcephaly, renal parenchymal disease, and simple cortical cysts. Whole exome sequencing (WES) revealed a novel mutation in the OTUD6B gene, as well as a previously known mutation in the PKD1 gene, explaining the blended phenotype observed in the patient.