Craniosynostosis

Gene: TMCO1

Green List (high evidence)

TMCO1 (transmembrane and coiled-coil domains 1)
EnsemblGeneIds (GRCh38): ENSG00000143183
EnsemblGeneIds (GRCh37): ENSG00000143183
OMIM: 614123, Gene2Phenotype
TMCO1 is in 8 panels

3 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Rare syndrome with macrocrania. CSS shown in 2/11 FMs in a large pedigree (Xin et al 2010). Pehliva report a case with frontotemporal atrophy on cranial MRI. Alanay et al 2013 report a case with prominent metopic suture. ; Review on behalf of Tracy Lester and Andrew Wilkie
Created: 5 Mar 2019, 11:33 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebrofaciothoracic dysplasia/ craniofacial dysmorphism, skeletal anomalies and MR syndrome

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Promoting from red to green as there are 3 cases reported with craniosynostosis as a feature.
Created: 14 Aug 2019, 1:52 p.m. | Last Modified: 14 Aug 2019, 1:52 p.m.
Panel Version: 1.125
Associated with Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome (#213980) in OMIM and Gene2Phenotype (confirmed)

PMID: 20018682 - Xin et al 2010 - identified an autosomal recessive condition in 11 individuals in the Old Order Amish of northeastern Ohio. The syndrome was characterized by distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation. They identified a homozygous frameshift mutation, c.139_140delAG, in TMCO1 in all affected members of the extended pedigree. 2 of the 11 individuals showed craniosynostosis.

PMID: 24424126 - Pehlivan et al 2014 - report a patient with cerebro-facio-thoracic dysplasia with a homozygous splice-site mutation TMC01 identified using WES. Cranial MRI revealed frontotemporal atrophy, dilated lateral ventricles and a short, dysgenetic corpus callosum.

PMID: 24194475 - Alanay et al 2013 - identified a homozygous nonsense founder mutation, p.Arg87Ter (c.259 C>T), in TMCO1 in 4 families of Turkish origin with Cerebrofaciothoracic dysplasia. Patient 4 from family 2 had a Prominent metopic suture (craniosynostosis).

3 cases with craniosynostosis reported.

Other cases have been reported, but without craniosysnosotis e.g. PMID: 23320496, PMID: 31102500, PMID: 30556256
Created: 14 Aug 2019, 1:48 p.m. | Last Modified: 14 Aug 2019, 1:55 p.m.
Panel Version: 1.126
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: TMCO1; Suggested initial gene rating: green
Created: 5 Mar 2019, 11:21 a.m.

Andrew Wilkie (University of Oxford)

Red List (low evidence)

Rare syndrome with macrocrania, brachycephaly, hypoplasia of corpus callosum, enlargement of septum pellicidum, diffuse hypodensity of grey matter, flat face, hypertelorism, cleft lip/palate, low-set, posteriorly rotated ears, short neck, and multiple costal and vertebral anomalies
Created: 15 Sep 2015, 9:27 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
cerebrofaciothoracic dysplasia

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • MR syndrome
  • Cerebrofaciothoracic dysplasia/ craniofacial dysmorphism
  • skeletal anomalies
  • Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, 213980
OMIM
614123
Clinvar variants
Variants in TMCO1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

14 Aug 2019, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TMCO1 were changed from MR syndrome; Cerebrofaciothoracic dysplasia/ craniofacial dysmorphism; skeletal anomalies to MR syndrome; Cerebrofaciothoracic dysplasia/ craniofacial dysmorphism; skeletal anomalies; Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, 213980

14 Aug 2019, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TMCO1 were set to

14 Aug 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tmco1 has been classified as Green List (High Evidence).

11 May 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Added phenotypes MR syndrome; Cerebrofaciothoracic dysplasia/ craniofacial dysmorphism; skeletal anomalies for gene: TMCO1

5 Mar 2019, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to TMCO1.

1 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

1 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

15 Sep 2015, Gel status: 0

Added New Source

Andrew Wilkie (University of Oxford)

TMCO1 was added to Craniosynostosis syndromes phenotypespanel. Sources: Expert Review