A novel nonsense mutation of ZEB2 gene in a Chinese patient with Mowat‐Wilson syndrome

BACKGROUND: Mowat‐Wilson syndrome (MWS) is a rare genetic disorder characterized by intellectual disability, distinctive facial features, and multiple anomalies caused by haploinsufficiency of the ZEB2 gene. We investigated the genetic causes of MWS in a 14‐year‐old girl who had characteristic features of MWS. METHODS: Clinical data and peripheral blood DNA samples were collected from the proband. Following extraction of genomic DNA, whole‐exome sequencing was conducted to detect genetic variants. Bioinformatics analysis was carried out to predict the function of the mutant gene. RESULTS: Mutation analysis of the proband identified a novel nonsense mutation (c.250G > T, p.E84*) within exon 3 of the ZEB2 gene. This novel alteration resulted in a termination codon at amino acid position 84, which was predicted to encode a truncated protein. This variant was not present in unrelated healthy control samples that were obtained from the exome sequence databases ExAc browser (http://exac.broadinstitute.org/) and gnomAD browser (http://gnomad.broadinstitute.org/). It is a novel variant that was determined to be a deleterious mutation according to the variant interpretation guidelines of the ACMG. The results of our study suggest that the p.E84* mutation in the ZEB2 gene was probably the pathogenic mutation that caused MWS in the proband. CONCLUSIONS: This study reports the novel mutation in the proband will provide a basic foundation for further investigations to elucidate the ZEB2‐related mechanisms of MWS.