Rare Turner syndrome and lupus coexistence with insights from DNA methylation patterns

Systemic lupus erythematosus (SLE or lupus) is a complex autoimmune disease that can affect multiple organs. While the exact disease etiology remains incompletely understood, there is a suggested influence of X-chromosome dosage in the pathogenesis of lupus. Here, we report a rare case of a female patient diagnosed with mosaic Turner syndrome and subsequently presenting with juvenile-onset SLE. DNA methylation patterns were analyzed in this patient and compared with age-matched female SLE controls, revealing higher methylation levels in interferon-regulated genes previously shown to be hypomethylated in SLE. These data provide a potential link between a gene-dose effect from the X-chromosome and the lupus-defining epigenotype. We hypothesize that the attenuated demethylation in interferon-regulated genes might provide a protective effect explaining the rarity of SLE in Turner syndrome. •A rare coexistence of Turner syndrome and lupus is reported.•Turner syndrome is associated with an attenuated lupus-associated epigenetic signature.•Epigenetics suggests a mechanistic explanation for the rarity of lupus in Turner syndrome.•Autosomal DNA methylation is linked to the gene-dose effect on the X-chromosome.