Submission Details

The DDX11 gene is located on chromosome 12 at 12p11.21 and encodes the DEAD/H-Box Helicase 11, which is involved in the maintenance of genomic stability and cohesion of chromosome arms and centromeres in nucleocytoplasm or in mitotic phase. DDX11 was first reported in relation to autosomal recessive Warsaw breakage syndrome in 2010 (van der Lelij et al. 2010, PMID: 20137776). Warsaw breakage syndrome is a rare disorder with typical clinical features including growth delay, facial dysmorphia, microcephaly, hearing loss due to cochlear malformations and, at cytological level, sister chromatid cohesion defects. Eighteen variants (ten missense, three frameshift, two nonsense, one intronic, one deletion, and one insertion) have been reported in 11 probands in six publications (PMIDs: 20137776, 23033317, 30216658, 30924321, 32855419, 36703504). The mechanism of pathogenicity at this time is reported to be loss of function. This gene-disease relationship is also supported by functional alteration in patient cells, rescue in patient cells, biochemical function studies, and a zebrafish model (PMIDs: 20137776, 26089203). In summary, there is definitive evidence supporting the relationship between DDX11 and autosomal recessive Warsaw breakage syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date February 21st, 2025 (SOP Version 11).