[Clinical features and genetic analysis of two children with Mowat-Wilson syndrome due to variants of ZEB2 gene].

Objective: To explore the clinical features and genetic variants in two children with Mowat-Wilson syndrome (MWS).

Methods: Two children admitted to the Affiliated Women and Children's Hospital of Ningbo University respectively in May and October 2022 were selected as the study subjects. Clinical data of the patients were collected. The two children were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of the Women and Children's Hospital of Ningbo University (Ethic No.EC2020-014).

Results: Child 1 was a 3-year-old male who had presented with epilepsy. Cranial MRI revealed hypoplasia of corpus callosum, down-slanting eyes, hypotonia, developmental delay, and recurrent constipation. The child was found to harbor a de novo c.262dup (p.Ile88Asnfs*31) missense variant of the ZEB2 gene, which was detected in neither parents. Child 2 was a 6-months-old male presented with epilepsy, with no apparent anomaly detected by cranial MRI. The child had featured developmental delay, inverted eyelash, atrial septal defect, and cryptorchidism. WES revealed that he had harbored a c.3213_3224delinsCTAC (p.Q1072Yfs*49) frameshifting variant of the ZEB2 gene, which was detected in neither parents. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were determined as likely pathogenic, with ratings of PVS1_Strong+PM2_Supporting+PM6 and PVS1_Strong+PM2_Supporting+PM6. Both variants had resulted in premature occurrence of stop codons.

Conclusion: By combining their clinical features and results of genetic testing, both children had been diagnosed with MWS due to variants of the ZEB2 gene. Above findings have enriched the mutational spectrum of MWS and provided a basis for the prenatal diagnosis and genetic counseling.