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De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in the<jats:italic>SETD1B<\/jats:italic>gene which may be used as an epigenetic marker supporting the diagnosis of syndromic<jats:italic>SETD1B<\/jats:italic>-related diseases. 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