MED12 missense mutation in a three-generation family. Clinical characterization of MED12-related disorders and literature review

Abstract Mutations in MED12 gene have been described in association with syndromic and non-syndromic X-linked intellectual disability (XLID). Up to date at least three distinct XLID syndromes have been described: FG syndrome, Lujan-Fryns syndrome (LS) and Ohdo syndrome (OSMKB). In the last years, thanks to the massive use of next generation sequencing techniques (NGS) it has been possible to discover at least 16 others MED12 mutations and to expand the phenotype of MED12-related disorders. Here we report three subjects from a large non-consanguineous family presenting with a mild to severe ID, important speech delay, behavior problems, dysmorphic facial features and hearing loss. NGS allows us to detect the MED12 missense variant c.3883C > T (p.(Arg1295Cys)) carried by the three patients. This variant has been reported in 2016 by Hu et al. in one family from a big cohort of XLID families. This clinical report contributes to expanding the phenotype associated with MED12-mutations.