Middle interhemispheric variant of holoprosencephaly: First prenatal report of a ZIC2 missense mutation

Abstract

We present a case of a middle interhemispheric variant of antenatal discovery associated with a de novo missense variant (NM_007129.5: c.1109G>A p.(Cys370Tyr)) in the ZIC2 gene. Our case represents the first prenatal description of a ZIC2 missense mutation found in association with syntelencephaly.

Keywords: ZIC2; middle interhemispheric variant of holoprosencephaly; missense mutation; syntelencephaly.

FIGURE 1

A, Midsagittal slice showing the agenesis of the posterior part of the corpus callosum, the fused parenchyma on the midline (arrow), and the retrocerebellar arachnoid cyst (arrow head). B, Coronal slice through the third ventricle showing the parenchymal bridge (arrow). C, D, Axial slices showing the cerebellar hypoplasia (C) and the parenchymal bridge (D, arrow)

FIGURE 2

A, De novo c.1109G>A p.(Cys370Tyr) variant in exon 2 of the ZIC2 gene visualized in IGV. B, Presence of the mutation in the fetus but none of the parent was confirmed by Sanger sequencing. C, Schematic representation of the ZIC2 gene and its protein (with the main protein domains) along with the mutation described in MIHV until now (data collected from Ref.14, 15). Our missense mutation is shown in red