Malformations of cortical development

Gene: ZNF865

Green List (high evidence)

Comment on list classification: There are 8 individuals reported in literature with heterozygous ZNF865 variants and brain abnormalities, including hypoplasia of corpus callosum and ventriculomegaly. Based on available evidence, this gene should be promoted to Green at the next GMS update.

Created: 10 Mar 2026, 1:37 p.m. | Last Modified: 10 Mar 2026, 1:37 p.m.

Panel Version: 7.34

PMID: 40936200 Bradbrook et al., 2025
Report of 18 unrelated individuals (Caucasian / Latino ethnicity) with developmental delay and shared dysmorphic features, harbouring heterozygous variants in ZNF865. Method: WGS / WES. Majority described as severely delayed, with speech delay and moderate to severe learning difficulties; avg age of walking = 24 months, 9/18 patients presented with hypotonia, 1 patient diagnosed with epilepsy, 9/15 had digit anomalies.
On MRI, 8/14 patients had brain abnormalities, including hypoplasia of corpus callosum and ventriculomegaly. Shared dysmorphic features: broad nasal bridge, hypertelorism, low-set ears.
14 unique variants (nonsense of frameshift) were detected, mostly towards the C-terminus. Variants were confirmed as de novo in 15 individuals.

This gene is not yet linked to any phenotype in OMIM (accessed 10th Mar 2026).
Sources: Literature

Created: 10 Mar 2026, 1:36 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 40936200