Missense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes
Authors:
Open Access
- 22 October 2022
- journal article
- research article
- Published by Wiley in American Journal of Medical Genetics Part A
- Vol. 191 (1) , 135-143
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, 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 challenging. Therefore, we think that patients with a causative MED12 variant are currently underdiagnosed due to the broad patients' clinical presentations.Keywords
Funding Information
- Broad Institute
- National Eye Institute
- National Human Genome Research Institute (R01 HG009141)
This publication has 27 references indexed in Scilit:
- A novel MED12 mutation associated with non-specific X-linked intellectual disabilityHuman Genome Variation, 2015
- Nonsyndromic X‐linked intellectual deficiency in three brothers with a novel MED12 missense mutation [c.5922G>T (p.Glu1974His)]Clinical Case Reports, 2015
- X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genesMolecular Psychiatry, 2015
- Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disabilityClinical Genetics, 2013
- Mutations in MED12 Cause X-Linked Ohdo SyndromeThe American Journal of Human Genetics, 2013
- Fragile X and X-Linked Intellectual Disability: Four Decades of DiscoveryThe American Journal of Human Genetics, 2012
- A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndromeNature Genetics, 2007
- The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 geneJournal of Medical Genetics, 2007
- Spectrum of disease-causing mutations in protein secondary structuresBMC Structural Biology, 2007
- Protein Stability and Surface Electrostatics: A Charged RelationshipBiochemistry, 2006