Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome

Gene: GTF2E2

Amber List (moderate evidence)

GTF2E2 (general transcription factor IIE subunit 2)
EnsemblGeneIds (GRCh38): ENSG00000197265
EnsemblGeneIds (GRCh37): ENSG00000197265
OMIM: 189964, Gene2Phenotype
GTF2E2 is in 7 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Four individuals from 3 different Moroccan families with the same homozygous variant (c.C559T) in the GTF2E2 gene have been identified who all presented with non-photosensitive trichothiodystrophy. Even though this likely represents a founder effect in this population, an additional patient from Asian origin has been identified with a distinct homozygous variant (c.448G>C), corroborating pertinence of GTF2E2 variants in trichothiodystrophy. Furthermore, studies on primary fibroblasts of patients harbouring the founder variant demonstrated a reduction in the cellular levels of both subunits of the transcription initiation factor TFIIE.

Overall this is sufficient evidence to promote this gene to Green at the next GMS panel update.
Created: 30 Sep 2021, 1:23 p.m. | Last Modified: 30 Sep 2021, 1:23 p.m.
Panel Version: 2.10

Michael Yau (Genetics, Viapath)

Green List (high evidence)

GTF2E2 is currently an amber gene in R227 and the evidence for it being included was "2 cases reported in OMIM from one publication (Kuschal et al, 2016). It is a probable DD gene for DNA Repair-Proficient Trichothiodystrophy."

In the two reported cases by Kuschal et al (2016) the following likely pathogenic variants in two unrelated individuals (TTD379BE and TTD28PV) with non-photosensitive TTD (NPS-TTD) were detected: 1) TTD379BE: Homozygous GTF2E2 c.448G>C p.(Ala150Pro) and 2) TTD28PV: Homozygous GTF2E2 c.559G>T p.(Asp187Tyr). In 2017, Theil et al reported the same homozygous missense variant, GTF2E2 c.559C>T, p.(Asp187Tyr) in two unrelated NPS-TTD Moroccan individuals. Functional studies by Theil et al (2017) show that this variant greatly reduces the total amount of the entire TFIIE complex. It also appears that the variant has a temperature-sensitive transcription defect, that appears to correlate with the phenotypic worsening of key clinical symptoms after episodes of high fever. This is a total of four unrelated families with pathogenic variants in the GTF2E2 that supports this gene's association to NPS-TTD.
Created: 13 Sep 2021, 2:54 p.m. | Last Modified: 13 Sep 2021, 2:54 p.m.
Panel Version: 2.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Trichothiodystrophy 6, nonphotosensitive:

Publications

Ellen McDonagh (Genomics England Curator)

Comment on list classification: 2 cases reported in OMIM from one publication (Kuschal et al, 2016). It is a probable DD gene for DNA Repair-Proficient Trichothiodystrophy.
Created: 28 Nov 2016, 5:10 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Trichothiodystrophy 6, nonphotosensitive; 616943

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
Phenotypes
  • Trichothiodystrophy 6, nonphotosensitive, OMIM:616943
Tags
Q3_21_rating
OMIM
189964
Clinvar variants
Variants in GTF2E2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

30 Sep 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_21_rating tag was added to gene: GTF2E2.

30 Sep 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: GTF2E2 were set to 26996949

30 Sep 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: GTF2E2 were changed from Trichothiodystrophy 6, nonphotosensitive; 616943 to Trichothiodystrophy 6, nonphotosensitive, OMIM:616943

30 Sep 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: gtf2e2 has been classified as Amber List (Moderate Evidence).

28 Nov 2016, Gel status: 2

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

28/Nov/2016: Panel combined and revised due to external and internal review.

28 Nov 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for GTF2E2 were set to 26996949

28 Nov 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

28 Nov 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

28 Nov 2016, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

GTF2E2 was added to Cockayne and Xeroderma Pigmentosum-like disorderspanel. Sources: Other

28 Nov 2016, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

GTF2E2 was created by ellenmcdonagh