[Report of a child with Bainbridge-Ropers syndrome due to a novel variant of ASXL3 gene and a literature review].

OBJECTIVE

To explore the clinical phenotype and genetic basis of a child with Bainbridge-Ropers syndrome (BRPS).

METHODS

A child with BRPS who had visited Nanjing Children's Hospital on June 26, 2019 was selected as the study subject. Clinical data of the child was reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.

RESULTS

The child was a 6-month-old girl with peculiar facial features, feeding difficulties, malnutrition, global developmental delay, hypotonia, mildly elevated aminotransferase and ulnar deviation. Results of WES showed that she has harbored a c.1533_1534del variant of the ASXL3 gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. No similar case had been retrieved from the HGMD and ClinVar databases. No frequency for this variant among Asian populations was available in the ExAC, 1000 Genomes, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1533_1534del variant of the ASXL3 gene was determined to be likely pathogenic (PVS1+PS2+PM2_Supporting).

CONCLUSION

The ASXL3 gene c.1533_1534del variant probably underlay the BRPS in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling for children with similar disorders.