Genes in panel

Ataxia and cerebellar anomalies - narrow panel

Gene: THG1L

Amber List (moderate evidence)

THG1L (tRNA-histidine guanylyltransferase 1 like)
EnsemblGeneIds (GRCh38): ENSG00000113272
EnsemblGeneIds (GRCh37): ENSG00000113272
THG1L is in 2 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: Ataxia only reported in 3 Ashkenazi Jewish families with the same p.V55A founder variant. Unclear whether the fourth case with a different variant (p.L294P) displayed ataxia. Therefore, additional cases or functional analysis of the p.V55A variant are required prior to upgrading this gene to Green.
Created: 1 Mar 2021, 2:59 p.m. | Last Modified: 1 Mar 2021, 2:59 p.m.
Panel Version: 2.50
Associated with relevant phenotype in OMIM (MIM# 618800), but not yet in Gene2Phenotype.

- PMID: 27307223 (2016) - Homozygous p.V55A variant identified in three sibs of Ashkenazi Jewish descent with cerebellar signs including ataxia, developmental delay, dysarthria, pyramidal signs and cerebellar atrophy on brain MRI. Patient fibroblasts displayed abnormalities in mitochondrial fusion with increased fragmentation compared to controls when cultured with galactose.

- PMID: 31168944 (2019) - The same homozygous p.V55A variant detected in two additional unrelated Ashkenazi Jewish patients. Clinical features include developmental delay, ataxic gait, spasticity, and uncoordinated movements. No functional studies were performed.

- PMID: 30214071 (2019) - One individual with a homozygous missense variant (p.L294P) in THG1L ascertained from a congenital microcephaly cohort. Phenotypes include IUGR, GDD, epilepsy, autoimmune thrombocytopenia, transient neutropenia, and optic atrophy. Authors do note diffuse cerebral and cerebellar atrophy on brain imaging; however, it is unknown whether the individual exhibited any ataxic features.
Created: 1 Mar 2021, 2:51 p.m. | Last Modified: 1 Mar 2021, 2:51 p.m.
Panel Version: 2.49

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Four Ashkenazi Jewish families reported, with same homozygous variant, p.V55A in affected individuals. Another individual from different ethnicity also reported. A carrier rate of 0.8%, but no THG1L V55A homozygotes, was found in a cohort of 3,232 unrelated Ashkenazi Jewish individuals, and no homozygotes found in Exac or gnomAD.
Sources: Literature
Created: 1 May 2020, 10:11 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebellar ataxia

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800
  • Spinocerebellar ataxia, autosomal recessive 28, MONDO:0032923
Tags
watchlist
Clinvar variants
Variants in THG1L
Penetrance
None
Publications
Panels with this gene

History Filter Activity

1 Mar 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: THG1L.

1 Mar 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: THG1L were changed from Cerebellar ataxia to Spinocerebellar ataxia, autosomal recessive 28, OMIM:618800; Spinocerebellar ataxia, autosomal recessive 28, MONDO:0032923

1 Mar 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: thg1l has been classified as Amber List (Moderate Evidence).

1 May 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: THG1L was added gene: THG1L was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: THG1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: THG1L were set to 27307223; 30214071; 31168944 Phenotypes for gene: THG1L were set to Cerebellar ataxia Review for gene: THG1L was set to GREEN