Non-syndromic familial congenital anorectal malformations

Gene: MED12

Green List (high evidence)

MED12 (mediator complex subunit 12)
EnsemblGeneIds (GRCh38): ENSG00000184634
EnsemblGeneIds (GRCh37): ENSG00000184634
OMIM: 300188, Gene2Phenotype
MED12 is in 11 panels

2 reviews

Charles Shaw-Smith (Royal Devon and Exeter NHS Trust)

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
FG syndrome

Eleanor Williams (Genomics England Curator)

Note that in Gene2Phenotype the Mutation consequence summary is "uncertain".
Created: 1 Nov 2018, 1:12 p.m.
Comment on list classification: Rated green as more than 3 families with the R961W variant show a relevant phenotype.
Created: 8 Oct 2018, 8:39 p.m.
MED12 is associated with Opitz-Kaveggia syndrome (also known as FG syndrome and FG syndrome 1) in OMIM and Gene2Phenotype (confirmed). Opitz-Kaveggia syndrome (OKS) is an X-linked recessive mental retardation syndrome characterized by dysmorphic features, but phenotypes relevant to this panel also include anal stenosis, imperforate anus, anteriorly placed anus and constipation.

As stated in OMIM Risheg et al 2007 (PMID: 17334363) reported that the original family from which the designation FG was derived and 5 other families had a recurrent mutation in the MED12 gene, R961W. Imperforate anus, wide flat thumbs, and wide great toes were present in 7 of 10 cases. Failure to find the change in 451 normal men and in 343 consecutive newborn males suggested that it is not a rare polymorphic variant. The finding of the mutation in patients of various ethnic backgrounds suggested that families did not share a common ancestor.

Ding et al. (2008) (PMID: 18691967) showed that the R961W substitution disrupts the REST corepressor function of MED12.

Other variants in MED12 are linked to other syndromes such as LUJAN-FRYNS SYNDROME and OHDO SYNDROME, X-LINKED.
Created: 8 Oct 2018, 8:38 p.m.
Comment on list classification: Rated gene amber as is on expert list
Created: 19 Sep 2018, 4:19 p.m.
Gene added from expert list from Dr Charles Shaw-Smith (Royal Devon and Exeter NHS Foundation Trust) who has associated it with FG syndrome (also known as Opitz-Kaveggia syndrome)
Created: 19 Sep 2018, 4:19 p.m.

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • anorectal malformation
  • Opitz-Kaveggia syndrome 305450
  • FG SYNDROME 1
  • FG SYNDROME
OMIM
300188
Clinvar variants
Variants in MED12
Penetrance
None
Publications
Panels with this gene

History Filter Activity

8 Nov 2018, Gel status: 3

Panel promoted to version 1.0

Eleanor Williams (Genomics England Curator)

Eleanor Williams: Gene added from expert list fr

1 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: med12 has been classified as Green List (High Evidence).

8 Oct 2018, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: MED12 were changed from anorectal malformation to anorectal malformation; Opitz-Kaveggia syndrome 305450; FG SYNDROME 1; FG SYNDROME

8 Oct 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MED12 were set to

8 Oct 2018, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: MED12 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females

8 Oct 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: med12 has been classified as Green List (High Evidence).

19 Sep 2018, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: med12 has been classified as Amber List (Moderate Evidence).

19 Sep 2018, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Added phenotypes anorectal malformation for gene: MED12

19 Sep 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: MED12 was added gene: MED12 was added to Non-syndromic familial congenital anorectal malformations. Sources: Expert list Mode of inheritance for gene: MED12 was set to Phenotypes for gene: MED12 were set to anorectal malformation