Missense 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, chi(2) test), but mostly outside the functional domains (p = 0.004; chi(2) 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 challenging. Therefore, we think that patients with a causative MED12 variant are currently underdiagnosed due to the broad patients' clinical presentations.

Automated summary

We described the phenotype of 22 male patients (20 probands) with a hemizygous missense variant in the MED12 gene. The phenotypic spectrum ranges from nonspecific intellectual disability to well-known syndromes. The identified variants were randomly distributed throughout the gene but mostly outside the functional domains. Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants or the protein domain involved. In conclusion, establishing a genotype-phenotype correlation in MED12-related diseases remains challenging, and patients with a causative MED12 variant may be underdiagnosed due to their diverse clinical presentations. Rating: 9/10