Four heterozygous variants in identified with Bainbridge-Ropers syndrome and further dissecting published genotype-phenotype spectrum.

Bainbridge-Ropers syndrome (BRPS) is a recently described neurodevelopmental genetic disorder associated with truncating variants in additional sex combs like 3 () on chromosome 18q12.1. Trio-based exome sequencing was conducted on patients admitted to the Children's Hospital Affiliated to Shandong University and diagnosed with unexplained intellectual disabilities or developmental delay between June 2022 and January 2024. truncation of was identified in four patients, and the pathogenic variants and their status were validated using Sanger sequencing. Comprehensive clinical phenotype-genotype information of all previously reported patients with BRPS was collected and summarized. The common clinical manifestations observed in the four patients included language and intellectual disabilities or psychomotor retardation. Genetic analysis revealed that patient 1 carried a heterozygous variant, c.1667_1668del (p.Thr556Arpfs3), whereas patient 2 had a novel heterozygous frameshift variant of , c.3324del (p.Lys1109Serfs34). These two variants have not been documented to date. Additionally, patients 3 and 4 exhibited a variant, c.4678C > T (p.Arg1560Ter). Based on the combined assessment of clinical phenotypes and genetic testing results, it was postulated that all four children presented with BRPS syndrome caused by pathogenic variations in . The present study complements the range of mutational and phenotypic spectra in the population, highlighting subtle distinctions in clinical manifestations between Chinese patients and other racial groups. The reporting of additional cases will contribute to further elucidating the function of and establishing a solid foundation for clinical diagnosis and treatment.