biostudies-literatureMaia NNational Eye InstituteNEI NIH HHSFoundation for Science and Technology (FCT)NHGRI NIH HHSBroad InstituteNational Human Genome Research Institute135-143https://www.ebi.ac.uk/biostudies/studies/S-EPMC10092556biostudies-literatureUnknown191(1)We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.993, χ² test), but mostly outside the functional domains (p = 0.004; χ² test). Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants (p = 0.295; Pearson correlation), nor the protein domain involved (p = 0.422; Pearson correlation). In conclusion, establishing a genotype-phenotype correlation in MED12-related diseases remains challenAmerican journal of medical genetics. Part AMissense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes.PMC10092556UIDB/00215/2020 UIDP/00215/2020 LA/P/0064/2020R01 HG009141UM1 HG008900Santos RTerhal PIbarluzea NKleefstra TYeh RCKoboldt DCValenzuela IKarteszi JMarcelis CLMMori MGabau Vila ESoares GJorge PMaia NMarques IElting MWNeil JECueto-Gonzalez AMMisra-Isrie MCsaszar ABessenyei BGuitart MKeski-Filppula RLasa-Aranzasti AAbu-Libde BChhouk BHde Brouwer APMvan Hagen JMHickey SLehman Avan Bokhoven HfalseMissense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes.We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.993, χ² test), but mostly outside the functional domains (p = 0.004; χ² test). Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants (p = 0.295; Pearson correlation), nor the protein domain involved (p = 0.422; Pearson correlation). In conclusion, establishing a genotype-phenotype correlation in MED12-related diseases remains challen2023-01-01T00:00:00Z2023 Jan2026-04-08T14:04:13.67Z2025-04-07T05:08:03.525ZS-EPMC100925563627181110.1002/ajmg.a.63004