Neurodevelopmental disorder of intellectual disability and epilepsy caused by ZNF142 mutation

We studied two affected individuals of a consanguineous Bedouin family that presented at infancy with an autosomal recessive syndrome of global developmental delay and epilepsy. Genome-wide linkage analysis identified a single ⁓5 Mbp likely disease-associated locus on chromosome 2q35. Whole exome sequencing (WES) identified three novel homozygous variants in three different genes within this locus. Two of the three variants were missense changes in genes previously associated with human diseases whose manifestations were not evident in the patients. Furthermore, those two variants were predicted to be non-deleterious using bioinformatics tools. Therefore, the third variant, a novel homozygous deletion mutation in zinc finger protein 142 (ZNF142) within this locus was identified as the likely disease-causing mutation. Our findings are in line with a parallel independent study published recently that identified homozygous mutations in ZNF142 as being associated with a neurodevelopmental syndrome of intellectual disability and epilepsy with or without dystonia. We are now studying in-vitro and through generation of transgenic mice the downstream molecular pathways by which the ZNF142 mutation causes the neurodevelopmental disorder, likely through ZNF142’s likely role as a transcriptional regulator.