Missense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes. Issue 1 (22nd October 2022)

• Record Type: Journal Article
• Authors: Maia, Nuno; Ibarluzea, Nekane; Misra‐Isrie, Mala; Koboldt, Daniel C.; Marques, Isabel; Soares, Gabriela; Santos, Rosário; Marcelis, Carlo L. M.; Keski‐Filppula, Riikka; Guitart, Miriam; Gabau Vila, Elisabeth; Lehman, April; Hickey, Scott; Mori, Mari; Terhal, Paulien; Valenzuela, Irene; Lasa‐Aranzasti, Amaia; Cueto‐González, Anna Maria; Chhouk, Brian H.; Yeh, Rebecca C.; Neil, Jennifer E.; Abu‐Libde, Bassam; Kleefstra, Tjitske; Elting, Mariet W.; Császár, Andrea; Kárteszi, Judit; Bessenyei, Beáta; van Bokhoven, Hans; Jorge, Paula; van Hagen, Johanna M.; de Brouwer, Arjan P. M.;
• Is Part Of: American journal of medical genetics. Volume 191:Issue 1(2023)
• Page Start: 135
• Page End: 143
• Publication Date: 2022-10-22
• Subjects: intellectual disability -- MED12 -- phenotype -- genotype; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.63004
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: 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, χ 2 test), but mostly outside the functional domains ( p = 0.004; χ 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.