DDX3X was first associated with X-linked syndromic intellectual disability as early as 2015 (Snijders Blok et al., PMID: 26235985). More than 100 unique variants have been reported in the literature (PMID: 32135084). Approximately half of the variants observed in humans are missense, although nonsense, frameshift, splice site, and in-frame indel variants have also been reported. Eight variants were included in this curation to reach a classification of definitive, however more evidence is available in the literature (PMID: 26235985, 30349862, 30936465, 30734472). Variants in this gene segregated with disease in 3 family members. More research is needed to determine whether disease is caused by haploinsufficiency or a dominant negative mechanism. This gene-disease association is supported by animal models, expression studies, and in vitro functional assays (PMID: 27179789, 27656019, 32135084). In summary, DDX3X is definitively associated with X-linked syndromic intellectual disability.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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