Expanding the phenotypic Spectrum of ZNF711: Autism and epilepsy in two siblings
Abstract
Zinc Finger Protein 711 (ZNF711) is a Krüppel-type zinc finger transcription factor highly expressed in the brain and whose mutations have been associated with neurodevelopmental disorders such as intellectual disability, autism spectrum disorder, and epilepsy. While most pathogenic variants previously described affect the C-terminal DNA-binding domain, we report two siblings carrying a rare hemizygous missense variant in the N-terminal transactivation domain, NM_001330574.2: c.65 T > C (p.Ile22Thr), inherited from their heterozygous unaffected mother. Patient #1 presents with autism spectrum disorder, epilepsy, moderate intellectual disability, and mild facial dysmorphisms, whereas Patient #2 shows milder autism spectrum disorder traits and no clinical seizures, although electroencephalogram abnormalities are present. In silico analyses predict that this variant, affecting a highly conserved residue, may disrupt protein structure and thus impair its proper function. The recurrence of this variant in the two siblings reported here and in those reported in Minerva et al. (2025) sharing overlapping phenotypes strengthens its potential pathogenicity, despite current classification as a variant of uncertain significance.
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