Fetal anomalies
Gene: TUBA8

TUBA8 (tubulin alpha 8)
EnsemblGeneIds (GRCh38): ENSG00000183785
EnsemblGeneIds (GRCh37): ENSG00000183785
OMIM: 605742, Gene2Phenotype
TUBA8 is in 13 panels

4 reviews

Arina Puzriakova (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 16 Mar 2022, 3:35 p.m. | Last Modified: 16 Mar 2022, 3:35 p.m.

Panel Version: 1.843

Created: 16 Mar 2022, 3:35 p.m.
Last Modified: 16 Mar 2022, 3:35 p.m.
Panel version: 1.843

Catherine Snow (Genomics England)

Comment on list classification: Change from Amber to Green, as requested by NHSE for signed-off panel.
Created: 19 Aug 2020, 6:24 p.m. | Last Modified: 19 Aug 2020, 6:24 p.m.

Panel Version: 1.88

Created: 19 Aug 2020, 6:24 p.m.
Last Modified: 19 Aug 2020, 6:24 p.m.
Panel version: 1.88

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Two families reported initially (PMID 19896110). However, note that mouse model does not have a brain phenotype and WES in the original families identified homozygous, previously reported as pathogenic, LoF variant in SNAP29, which is much more likely to be causative (28388629).
Created: 2 Mar 2020, 3:56 a.m. | Last Modified: 2 Mar 2020, 3:56 a.m.

Panel Version: 1.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cortical dysplasia, complex, with other brain malformations 8, MIM# 613180

Publications

Created: 2 Mar 2020, 3:56 a.m.
Last Modified: 2 Mar 2020, 3:56 a.m.
Panel version: 1.3

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

Comment on list classification: The reanalysis in PMID:28388629 casts doubt that TUBA8 is responsible for the morphological phenotypes initially reported in PMID:19896110. Only 2 families (of possible shared descent) were reported. Therefore insufficient evidence for Green rating. Downgraded from Green to Amber.
Created: 5 May 2020, 2:59 p.m. | Last Modified: 5 May 2020, 2:59 p.m.

Panel Version: 1.41

In 4 affected members of 2 consanguineous Pakistani families with MIM:613180, Abdollahi et al. (2009, PMID:19896110) identified a homozygous 14-bp deletion 11 bp upstream of the exon 2 splice site junction in TUBA8. The families may have common ancestory. All obligate carriers were heterozygous. The patients had neonatal hypotonia, profound mental retardation, essentially no psychomotor development, optic nerve hypoplasia, and thickened cortex with polymicrogyria and absent corpus callosum. BUT due to lack of a mouse TUBA8 phenotype, the authors in PMID:28388629 (Diggle et al 2017) reanalysed their patients from PMID:19896110 and found an additional LOF variant in SNAP29 (p.Ser163Lysfs*6). The authors suggest that SNAP29 deficiency, rather than TUBA8 deficiency, may be responsible for the patient phenotypes.
Created: 5 May 2020, 2:55 p.m. | Last Modified: 5 May 2020, 2:55 p.m.

Panel Version: 1.40

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 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: keep on the Fetal anomalies panel as a Green gene.
Created: 4 Apr 2019, 2:03 p.m.

DDG2P rating in original PAGE list: Confirmed for POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA
Created: 11 Dec 2018, 9:05 a.m.

Created: 11 Dec 2018, 9:05 a.m.

Panel version: 1.40

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
PAGE DD-Gene2Phenotype

Phenotypes

POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA
Cortical dysplasia, complex, with other brain malformations 8, 613180

OMIM

605742

Clinvar variants

Variants in TUBA8

Penetrance

None

Publications

Panels with this gene

History Filter Activity

16 Mar 2022, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: tuba8 has been classified as Amber List (Moderate Evidence).

16 Mar 2022, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review was removed from gene: TUBA8.

19 Aug 2020, Gel status: 3

Entity classified by Genomics England curator

Catherine Snow (Genomics England)

Gene: tuba8 has been classified as Green List (High Evidence).

5 May 2020, Gel status: 2