P719: The power of multi-omics in confirming the pathogenicity of a DDX11 variant causing Warsaw syndrome

UPD15pat) in 2 cases (16.7%),Silver-Russel syndrome (UPD7mat) in 2 cases (16.7%), and 2 patients (16.7%) with UPD14.In 8 cases, microarray analysis revealed complete isodisomy involving chromosomes 2 (2 cases), 3, 4, 6 (2 cases), 8, and 21.Out of 56 cases, 18 presented chromosome abnormalities (32.1%); additional chromosomal gains and losses were detected and consistent with their clinical phenotype.Notably, 2 patients exhibited mosaicism for whole chromosome aneuploidy, including UPD8 with trisomy 8 in 20% of cells, and UPD7 with mosaic monosomy 7 and isodisomy in a patient with myelodysplastic syndrome.Thus, in 30 patients (53.6%) either imprinting disorder and/or a chromosomal abnormality provided a diagnosis.Next generation or single gene sequencing studies were performed in 21 patients and detected pathogenic homozygous variants in 5/56 (9%) cases.Of the remaining cases, exome sequencing was either negative, or in 9 (16.1%)cases had homozygous or heterozygous variants of uncertain significance (VUS), or de novo likely pathogenic or de novo VUS variants.Conclusion: Our study shows that scROHs are commonly associated with imprinting or chromosomal conditions explaining the cause of developmental delay and congenital birth defects.Finding of scROH may indicate an imprinting condition, recessive disease, chromosomal abnormality or a combination of all.Our findings underscore the importance of detecting UPD through advanced microarray techniques and the need for specific diagnostic strategies.The concurrent presence of chromosomal abnormalities, such as aneuploidy and CNVs, may further complicate the diagnostic landscape in patients with these genomic features.