ClinGen Dosage Sensitivity Curation Page
MED13L
- Curation Status: Complete
- id: ISCA-21137
- Date last evaluated: 2015-11-11
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about MED13L at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/23389
- OMIM: https://omim.org/entry/608808
- ClinGen Haploinsufficiency Score: 3
- ClinGen Triplosensitivity Score: 1
- ExAC pLI score: 1.0
Select assembly:
(NC_000012.11)
(NC_000012.12)
- Haploinsufficiency score: 3
- Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
- Haploinsufficiency Phenotype: MENTAL RETARDATION AND DISTINCTIVE FACIAL FEATURES WITH OR WITHOUT CARDIAC DEFECTS; MRFACD
| 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
| 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. |