Fetal anomalies
Gene: MYT1

MYT1 (myelin transcription factor 1)
EnsemblGeneIds (GRCh38): ENSG00000196132
EnsemblGeneIds (GRCh37): ENSG00000196132
OMIM: 600379, Gene2Phenotype
MYT1 is in 3 panels

1 review

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: include on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: There is no disorder in OMIM assocaited with MYT1, but Oculo-auriculo-vertebral spectrum (OAVS, also called Goldenhar) is described in two papers from same group- PMID:28612832 and PMID:27358179. There are 3 MYT1 variants from these 2 papers (2 missense, 1 nonsense) in OAVS patients so just meets evidence threshold. Caution was taken given the genetic heterogeneity and non-genetic factors associated with OAVS/Goldenhar. However on balance it was decided that the 3 literature variants are sufficient evidence for inclusion of MYT1 on the Fetal anomalies panel.
Created: 29 Apr 2019, 2:52 p.m.

Berenguer et al 2017 (PMID:28612832) identified a third (de novo) MYT1 variant in a patient with OAVS: c.323C>T p.Ser108Leu from a cohort of 57 new patients with a typically heterogeneous OAVS. From functional studies, it's still unclear how these variants impact retinoic acid signaling and contribute to the phenotype.
Created: 25 Apr 2019, 2:58 p.m.

Lopez et al 2016 (PMID:27358179) identified a heterozgous MYT1 de novo nonsense variant in one patient (c.25C>T, p.Arg9*) and one heterozygous inherited missense variant in second patient (c.314C>T, p.Ser105Leu) in a cohort of 169patients with OAVS. Functional studies by transient knockdown of myt1a in zebrafish, led to specific craniofacial cartilage alterations.
Created: 25 Apr 2019, 2:58 p.m.

Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by hemifacial microsomia associated with ear, eyes and vertebrae malformations showing highly variable expressivity (PMID:28612832).
Created: 25 Apr 2019, 2:58 p.m.

MYT1 is not currently associated with a disorder in OMIM (April 2019) but there are two publications (PMID:28612832 and PMID:27358179) describing three separate variants in three patients with OAVS.
Created: 25 Apr 2019, 9:42 a.m.

MYT1 was added to the panel as Amber based on a 'Probable' rating in the Additional Gene list supplied by the PAGE group. Note that 'OAVS/Goldenhar syndrome' currently has a 'possible' rating in DD-G2P with Allelic requirement:monoallelic, and Mutation consequence summary:loss of function.
Created: 7 Mar 2019, 11:51 a.m.

Rating in original (Additional gene list) PAGE list: Probable. Original mode of inheritance: monoallelic. Original mode of pathogenicity: uncertain.
Created: 11 Dec 2018, 9:05 a.m.

In the original PAGE file, MOP listed as Uncertain.
Created: 8 Nov 2018, 4:45 p.m.

Publications

Mode of pathogenicity
Other - please provide details in the comments

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.225

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green
PAGE Additional Gene List

Phenotypes

Oculo-auriculo-vertebral spectrum (OAVS)
OAVS/Goldenhar syndrome

Tags

gene-checked

OMIM

600379

Clinvar variants

Variants in MYT1

Penetrance

None

Publications

Mode of Pathogenicity

Other

Panels with this gene

History Filter Activity

10 May 2022, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag gene-checked tag was added to gene: MYT1.

2 May 2019, Gel status: 4