ClinVar

Description

This mutation is denoted c.3499delA at the cDNA level and at the protein level is p.Ser1167ValfsX74; it is in exon 10 in the ZEB2 gene (NM_014795.3). The normal sequence with the base(s) that are deleted in braces is: AGAA{A}GTGA. This c.3499delA mutation in the ZEB2 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. The c.3499delA mutation causes a frameshift starting with codon Serine 1167, changes this amino acid to a Valine residue and creates a premature Stop codon at position 74 of the new reading frame, denoted p.Ser1167ValfsX74. This mutation is predicted to replace the last 48 amino acids of the protein with 73 incorrect residues. The lost region of the protein is well-conserved in mammals. The c.3499delA mutation was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.3499delA as a disease-causing mutation consistent with a diagnosis of Mowat-Wilson syndrome, an autosomal dominant disorder. This variant has been observed de novo with confirmed parentage. The variant is found in ZEB2 panel(s).