title: De novo mutations in genes of mediator complex causing syndromic intellectual disability: mediatorpathy or transcriptomopathy?
abstract: Mutations in the X-linked gene MED12 cause at least three different, but closely related, entities of syndromic intellectual disability. Recently, a new syndrome caused by MED13L deleterious variants has been described, which shows similar clinical manifestations including intellectual disability, hypotonia, and other congenital anomalies.
  
  
  
  Genotyping of 1,256 genes related with neurodevelopment was performed by next-generation sequencing in three unrelated patients and their healthy parents. Clinically relevant findings were confirmed by conventional sequencing.
  
  
  
  Each patient showed one de novo variant not previously reported in the literature or databases. Two different missense variants were found in the MED12 or MED13L genes and one nonsense mutation was found in the MED13L gene.
  
  
  
  The phenotypic consequences of these mutations are closely related and/or have been previously reported in one or other gene. Additionally, MED12 and MED13L code for two closely related partners of the mediator kinase module. Consequently, we propose the concept of a common MED12/MED13L clinical spectrum, encompassing Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, Ohdo syndrome, MED13L haploinsufficiency syndrome, and others.
authors: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Alfonso
authors: A
authors: Caro-Llopis
authors: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Monica
authors: M
authors: Rosello
authors: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Carmen
authors: C
authors: Orellana
authors: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Silvestre
authors: S
authors: Oltra
authors: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Sandra
authors: S
authors: Monfort
authors: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Sonia
authors: S
authors: Mayo
authors: Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Francisco
authors: F
authors: Martinez
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D019943:Amino Acid Substitution; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D056892:Mediator Complex / Q000235:genetics*; D050505:Mutant Proteins / Q000235:genetics; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D013577:Syndrome; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; C460107:MED12 protein, human; C480067:MED13L protein, human; D056892:Mediator Complex; D050505:Mutant Proteins