Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome
Gene: GTF2E2
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 31 Jan 2023, 4:31 p.m. | Last Modified: 31 Jan 2023, 4:31 p.m.
Panel Version: 2.27
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
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
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
Tag Q3_21_rating was removed from gene: GTF2E2.
Source Expert Review Green was added to GTF2E2. Source NHS GMS was added to GTF2E2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q3_21_rating tag was added to gene: GTF2E2.
Publications for gene: GTF2E2 were set to 26996949
Phenotypes for gene: GTF2E2 were changed from Trichothiodystrophy 6, nonphotosensitive; 616943 to Trichothiodystrophy 6, nonphotosensitive, OMIM:616943
Gene: gtf2e2 has been classified as Amber List (Moderate Evidence).
28/Nov/2016: Panel combined and revised due to external and internal review.
Publications for GTF2E2 were set to 26996949
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Red List (Low Evidence).
GTF2E2 was added to Cockayne and Xeroderma Pigmentosum-like disorderspanel. Sources: Other
GTF2E2 was created by ellenmcdonagh