Abstract
BACKGROUND: ZNF142 gene is a protein-coding gene encoding Zinc Finger Protein 142. ZNF proteins are a vast group of cellular effectors with a wide range of functions such as signal transduction, transcriptional regulation, meiotic recombination, DNA repair, development, and cell migration. Mutations in the ZNF142 gene are related to neurodevelopmental disorder with impaired speech and hyperkinetic movements (NEDISHM). This study on a family with three affected siblings identified a pathogenic frameshift insertion variant. In addition, we conducted a review of the literature on previously reported ZNF142 gene variants and their clinical manifestations. MATERIALS AND METHODS: Three affected siblings with severe intellectual developmental disabilities and speech impairments, their parents, and other sibs in the family were included. The patients were studied by the whole exome sequencing. Sanger sequencing, co-segregation analysis, and in silico analysis were carried out to verify candidate variant. The identified variant was interpreted based on the ACMG guideline. RESULTS: We identified a frameshift insertion variant in the ZNF142 gene, NM_001379659.1: c.3755dup (NP_001366588.1:p.Arg1253ThrfsTer15), that was related to the clinical features of three patients. The identified variant was found to be pathogenic. CONCLUSION: The current study findings expand the existing knowledge of the variant on the ZNF142 gene implicated in the neurodevelopmental disorder, intellectual disability, and impaired speech and it presents a detailed clinical feature associated with related conditions. The data have implications for genetic diagnosis and counseling in families with the same disorders.