[Clinical and genetic analysis of a child with MRXS34 syndrome due to variant of NONO gene].

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS). METHODS: A child diagnosed with BVSYS at Foshan Nanhai District Maternal and Child Health Care Hospital in January 2021 was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole genome sequencing (WGS) was carried out, and candidate variants were validated by Sanger sequencing. Pathogenicity of the candidate variants was evaluated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of the hospital (Ethics No.: 2025-01). RESULTS: The proband, a 4-year-and-5-month-old boy, presented with global developmental delay with intellectual disability, characteristic facial features, speech impairment, abnormal muscle tone, epilepsy, congenital heart disease, abnormal brain MRI findings, and microcephaly. WGS revealed that he has harbored compound heterozygous variants of the MED25 gene: (NM_030973.3) c.180+5G>C (maternal) and (NM_030973.3) c.394C>G (p.Arg132Gly) (paternal). Transcriptome sequencing confirmed that the c.180+5G>C variant may cause aberrant splicing with retention of intron 2. Based on the ACMG guidelines, this variant met the criteria PS3+PM2_Supporting+PP3 and was classified as likely pathogenic. The c.394C>G (p.Arg132Gly) variant resulted in an amino acid substitution and was predicted to be deleterious by in silico analysis. Based on the ACMG criteria (PM2_Supporting+PMS+PP3), it was classified as a variant of uncertain significance. A literature review showed that, among 23 BVSYS patients reported between 2015 and 2025, the most common clinical manifestations were developmental delay/intellectual disability and characteristic facial features (100%), followed by speech impairment (78.3%), abnormal muscle tone (60.8%), ocular abnormalities (60.8%), epilepsy (47.8%), and cardiac anomalies (47.8%). CONCLUSION: The c.180+5G>C and c.394C>G compound heterozygous variants of the MED25 gene probably underlay the pathogenesis of BVSYS in this child.