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Genetic epilepsy syndromes

Gene: TUBA8

Amber List (moderate evidence)

TUBA8 (tubulin alpha 8)
EnsemblGeneIds (GRCh38): ENSG00000183785
EnsemblGeneIds (GRCh37): ENSG00000183785
OMIM: 605742, Gene2Phenotype
TUBA8 is in 12 panels

3 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

Four cases from two consanguinous families had features including developmental delay and seizures- the same variant was identified in both families (PMID 19896110)
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cortical dysplasia complex with other brain malformations 8, 613180

Publications

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Amber.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment when marking as ready: Amber rating appropriate until further TUBA8 cases are confirmed. Added 'watchlist' tag.
Created: 3 Nov 2018, 10:32 a.m.
Comment on list classification: Kept rating as Amber. The phenotype is appropriate for the panel as seizures are part of MIM:613180, but insufficient cases for diagnostic rating. TUBA8 is a confirmed DD-G2P gene for 'POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA' (the former name for Cortical dysplasia, complex, with other brain malformations 8, 613180), and TUBA8 is on the UKGTN 43 gene panel for brain malformations. HOWEVER, the 4 literature cases (with all 4 patients showing seizures) come from 2 consanguineous families reported in one 2009 paper (PMID:19896110), and at least PMID:25008804 questions whether the families are related.

Leeds, Oxford (Usha Kini) and Cardiff genetic testing labs all confirmed (personal communication via email) that they have not seen any TUBA8 cases for their cortical malformations panel.

Based on this evidence, Helen Brittain, Clinical Fellow agreed on Amber rating for TUBA8.
Created: 3 Nov 2018, 10:30 a.m.
Fung et al (PMID:29588952, 2017) selected a cohort of 31 patients with seizure cryptogenic NIEE (neonatal/infantile epileptic encephalopathy). A compound heterozygous variant of uncertain significance was found in TUBA8 in a patient with severe ID, developmental regression, hypotonia and seizures. Unlike in the 2009 paper (PMID:19896110), no malformation of cortical development was seen.
Created: 24 Sep 2018, 3:46 p.m.
4 patients with 'Cortical dysplasia, complex, with other brain malformations 8, MIM:613180' were reported by Abdollahi et al. (2009, PMID:19896110). The 4 children come from 2 consanguineous Pakistani families, and all 4 children presented with seizures (infantile spasms or Tonic clonic). In both families, affected individuals harbour a homozygous 14bp deletion in TUBA8. Although the families were not knowingly related, at least PMID:25008804 questions if the families were indeed related.
Created: 24 Sep 2018, 2:59 p.m.
Comment on mode of inheritance: Biallelic MOI supported by G2P, OMIM and literature (PMID:19896110).
Created: 24 Sep 2018, 2:57 p.m.

Zornitza Stark (Australian Genomics)

I don't know

I can only find two reported families. Seizures are part of the phenotype in this brain development disorder.
Created: 22 Aug 2018, 7:24 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Wessex and West Midlands GLH
  • NHS GMS
  • Expert Review Amber
  • Victorian Clinical Genetics Services
Phenotypes
  • Cortical dysplasia, complex, with other brain malformations 8, 613180
  • seizures
Tags
watchlist
OMIM
605742
Clinvar variants
Variants in TUBA8
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Aug 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to TUBA8.

6 Aug 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to TUBA8.

11 Dec 2018, Gel status: 2

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: I can only find two reported f

3 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

3 Nov 2018, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: TUBA8 were changed from Cortical dysplasia, complex, with other brain malformations 8, 613180 to Cortical dysplasia, complex, with other brain malformations 8, 613180; seizures

3 Nov 2018, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: TUBA8.

3 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

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

24 Sep 2018, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: TUBA8 were set to 19896110; 27781032

24 Sep 2018, Gel status: 2

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: TUBA8 were set to

24 Sep 2018, Gel status: 2

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: TUBA8 was changed from to BIALLELIC, autosomal or pseudoautosomal

24 Sep 2018, Gel status: 2

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: TUBA8 were changed from to Cortical dysplasia, complex, with other brain malformations 8, 613180

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to TUBA8. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

TUBA8 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

TUBA8 was created by Sarah Leigh