ClinGen Dosage Sensitivity Curation Page

MED13L

  • Curation Status: Complete

Links

Location Information

  • 12q24.21
  • GRCh37/hg19 chr12: 116,396,381-116,714,991
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr12: 115,958,576-116,277,219
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000012.11) (NC_000012.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
24781760 van Haelst et al (2015) describe two individuals wit MED13L mutations. Patient 1 showed delayed milestones, sandal gap toe, facial asymmetry and macroglossia. Patient 2 presented with recurrent ear infections, speech and motor delay, short stature, and mild retrognathia. Whole exome sequencing of Patient 1 and her parents identified a de novo splice acceptor mutation in exon 5 that resulted in the use of a cryptic splice acceptor site 45 nucleotides into exon 5. This 45 bp deletion is in a highly conserved region of the protein and was presumed to disrupt gene product function. The analysis of Patient 2 by aCGH showed a 41 kb deletion of exons 6-20, also presumed to result in loss of function.
25712080 Cafiero et al (2015) report three individuals with de novo pathogenic variants detected by whole exome sequencing. In one patient, a 1 bp deletion in exon 17 was predicted to result in premature termination. In a second patient, a single base pair insertion in exon 5 was also predicted to result in premature termination, and in a third patient, a stop-gain variant was found. All three mutations are predicted to result in haploinsufficiency. The phenotypes of the patients is similar: dysmorphic features including a bulbous nasal tip with depressed nasal bridge, short mouth and straight eyebrows; developmental delay, motor delay, and intellectual disability.
25106414 Asadollahi et al (2013) report two individuals with de novo intragenic deletions and one individual with a 1 Mb triplication of the whole gene plus MAP1LC3B2. The deletion patients showed hypotonia, moderate intellectual disability, conotruncal heart defects, and facial anomalies. Patient 1 had a 17 kb deletion of exon 2. In silico studies showed the deletion to be out of frame. Patient 2 had a 115 kb deletion of exons 3 and 4, which was de novo by qPCR. Patient 3 showed a milder phenotype, with neonatal hypotonia, delayed walking and toilet training. Microarray using Affymetrix 6.0 platform showed a de novo 1 Mb triplication of all of MED13L and flanking gene, MAP1LC3B2.

Haploinsufficiency phenotype comments:

Additional loss-of-function mutations have been reported for MED13L in individuals with intellectual disability. See PMID: 23403903, 34896178, 25167861, 25356899

  • Triplosensitivity score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for gain of function phenotype
PubMed ID Description
25106414 Asadollahi et al (2013) report two individuals with de novo intragenic deletions and one individual (Pt 3) with a 1 Mb triplication of the whole MED13L gene plus MAP1LC3B2. Patient 3 showed a milder phenotype, with neonatal hypotonia, delayed walking and toilet training. Microarray using Affymetrix 6.0 platform showed a de novo 1 Mb triplication of all of MED13L and flanking gene, MAP1LC3B2.