Retinal disorders
Gene: MED12The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 8 Mar 2022, 10:43 a.m. | Last Modified: 8 Mar 2022, 10:43 a.m.
Panel Version: 2.245
Comment on mode of inheritance: X-linked hemizygous mutation in males, monoallelic mutations in females is the appropriate mode of inheritance for Hardikar syndrome but there are carrier implications for the male-only phenotypes associated with this gene (e.g. Lujan-Fryns syndrome, Ohdo syndrome, X-linked and Opitz-Kaveggia syndrome) in female cases.Created: 28 Sep 2021, 11:10 a.m. | Last Modified: 28 Sep 2021, 11:10 a.m.
Panel Version: 2.216
Comment on list classification: Promoting this gene from red to amber, but with a recommendation for green rating following GMS review. 5 cases reported with a retinal phenotype and likely disease causing variants in MED12.Created: 28 Sep 2021, 11:10 a.m. | Last Modified: 28 Sep 2021, 11:10 a.m.
Panel Version: 2.215
Zorntiza Stark reviewed this gene on the Clefting panel. Li et al 2021 (PMID: 33244166) report 7 females with Hardikar syndrome each of whom have had a nonsense or frameshift MED12 variant identified by exome sequencing. All five tested patients showed evidence of skewed x chromosome inactivation. 5 of the patients are reported to have a retinal phenotype (retinal rarefaction, pigmentary retinopathy, cat’s paw retinal pigmentation).
Hardikar syndrome is noted for the preserved neurodevelopment in patients unlike the other disorders associated with this gene.
Sources: LiteratureCreated: 28 Sep 2021, 11:08 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Hardikar syndrome, OMIM:612726; cholestasis-pigmentary retinopathy-cleft palate syndrome, MONDO:0012997
Publications
Tag Q3_21_MOI was removed from gene: MED12. Tag Q3_21_rating was removed from gene: MED12. Tag Q3_21_expert_review was removed from gene: MED12.
Source Expert Review Green was added to MED12. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q3_21_MOI tag was added to gene: MED12.
Tag Skewed X-inactivation tag was added to gene: MED12.
Tag Q3_21_rating tag was added to gene: MED12.
Mode of inheritance for gene: MED12 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Gene: med12 has been classified as Amber List (Moderate Evidence).
gene: MED12 was added gene: MED12 was added to Retinal disorders. Sources: Literature Q3_21_expert_review tags were added to gene: MED12. Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: MED12 were set to 33244166 Phenotypes for gene: MED12 were set to Hardikar syndrome, OMIM:612726; cholestasis-pigmentary retinopathy-cleft palate syndrome, MONDO:0012997 Review for gene: MED12 was set to GREEN