Fetal anomalies
Gene: MITF

MITF (melanogenesis associated transcription factor)
EnsemblGeneIds (GRCh38): ENSG00000187098
EnsemblGeneIds (GRCh37): ENSG00000187098
OMIM: 156845, Gene2Phenotype
MITF is in 9 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

This gene and phenotype were reviewed during meetings between November 2023 & July 2024. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler, Alison Male and Lyn Chitty (North Thames GLH), Stephanie Allen, Natalie Bibb, Esther Kinning and Denise Williams (Central & South GLH) and Natalie Canham, Anna De Burca and Samantha Doyle R21 Clinical Oversight Group.
Created: 29 Aug 2024, 8:33 p.m. | Last Modified: 29 Aug 2024, 8:33 p.m.

Panel Version: 4.36

Created: 29 Aug 2024, 8:33 p.m.
Last Modified: 29 Aug 2024, 8:33 p.m.
Panel version: 4.36

Natalie Chandler (North Thames GLH)

I don't know

Amber in Fetal anomalies panel on review in 2019. Autosomal recessive form only AD = waardenburg, albinism. Prev review: In 2 unrelated children with coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD; 617306), whose parents exihibited features of WS2A, George et al. (2016, PMID:27889061) identified compound heterozygosity for variants in the MITF gene. Agreed fetally relevant but insufficent cases for green. PMID:32541011 - Zebra fish functional study supporting AR phenotype. Keep amber - need more patients to go green.
Created: 29 Aug 2024, 8:07 p.m. | Last Modified: 29 Aug 2024, 8:07 p.m.

Panel Version: 4.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
COMMAD syndrome, OMIM:617306

Publications

Created: 29 Aug 2024, 8:07 p.m.
Last Modified: 29 Aug 2024, 8:07 p.m.
Panel version: 4.35

Rebecca Foulger (Genomics England curator)

I don't know

Kept rating as Amber on advice from Anna de Burca (Genomics England Clinical Team): fetally relevant phenotype but insufficient evidence for Green rating.
Created: 25 Jul 2019, 8:04 a.m. | Last Modified: 12 Aug 2019, 12:02 p.m.

Panel Version: 0.337

Comment on mode of inheritance: Changed MOI from 'both biallelic and monoallelic' to 'biallelic' as COMMAD phenotype has recessive inheritance, and COMMAD phenotype would present prenatally (see comment from Deirdre Cilliers).
Created: 11 Feb 2019, 4:03 p.m.

In 2 unrelated children with coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD; 617306), whose parents exihibited features of WS2A, George et al. (2016, PMID:27889061) identified compound heterozygosity for variants in the MITF gene.
Created: 11 Feb 2019, 4:01 p.m.

Communication from Deirdre Cilliers, Oxford University Hospitals (via email, February 2019): Yes [MITF should be on the Fetal anomalies panel]. COMMAD would present prenatally as microphalmia and congenital cataracts would be seen on ultrasound scan as may be the macrocephaly and frontal bossing. The parents would likely exhibit the Tietz albinism deafness/Waardenburg phenotypes so would be able to interpret variants for this condition. However, some fetusses may incidentally be identified to have Tietz albinism deafness/Waardenburg phenotypes, but this may also be informative to parents.
Created: 11 Feb 2019, 3:55 p.m.

'watchlist' tag added to highlight different DD-G2P ratings for this gene.
Created: 8 Nov 2018, 8:57 p.m.

In the original PAGE file: rated as Confirmed for WAARDENBURG SYNDROME TYPE 2 WITH OCULAR ALBINISM, TIETZ SYNDROME and WAARDENBURG SYNDROME TYPE 2A, and rated as Probable for Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness. In the original PAGE file, MOP listed as LOF for WAARDENBURG SYNDROME TYPE 2 WITH OCULAR ALBINISM, WAARDENBURG SYNDROME TYPE 2A and Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness, and listed as Uncertain for TIETZ SYNDROME.
Created: 8 Nov 2018, 4:45 p.m.

Created: 8 Nov 2018, 4:45 p.m.
Last Modified: 12 Aug 2019, 12:02 p.m.
Panel version: 0.311

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
PAGE DD-Gene2Phenotype

Phenotypes

COMMAD syndrome, OMIM:617306

Tags

watchlist

OMIM

156845

Clinvar variants

Variants in MITF

Penetrance

None

Publications

Panels with this gene

History Filter Activity

30 Aug 2024, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: MITF were changed from WAARDENBURG SYNDROME TYPE 2 WITH OCULAR ALBINISM; Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness; WAARDENBURG SYNDROME TYPE 2A; TIETZ SYNDROME; COMMAD syndrome, 617306; Tietz albinism-deafness syndrome, 103500; Waardenburg syndrome, type 2A, 193510; Waardenburg syndrome/ocular albinism, digenic, 103470 to COMMAD syndrome, OMIM:617306

30 Aug 2024, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: MITF were set to 27889061

11 Feb 2019, Gel status: 2