Cerebellar hypoplasia

Gene: TUBA8

Amber List (moderate evidence)

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

2 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Demoted from Green to Amber based on re-review of evidence. Demotion agreed by Clinical Fellow Helen Brittain.

TUBA8 was originally rated Green on the panel because 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:
https://ukgtn.nhs.uk/find-a-test/search-by-disorder-gene/brain-malformation-disorders-cortical-43-gene-panel-886/.

However, the reported evidence comes from one 2009 paper (PMID:19896110) with 4 literature cases coming from 2 consaguineous families (1 variant); at least PMID:25008804 questions whether the families are related. A 2017 paper identifies an additional VUS (compound heterozygous) in a chinese EE patient (PMID:29588952).

Anna de Burca confirmed that there are lots of cases with CNVs involving TUBA8 in DECIPHER but there are only two cases with SNVs in the gene. One of them is classified as unknown pathogenicity, the other likely benign.

I contacted Usha Kini at Oxford, and also the Leeds and Cardiff genetic testing groups (as recommended by Usha) since they all offer cortical malformation panels. All three confirmed (pers. comm. via email) that they have no further cases for TUBA8.

The literature evidence and communications from Oxford, Leeds and Cardiff all support demotion of TUBA8 to Amber rating: The phenotype is still appropriate for the panel but insufficient cases for diagnostic rating.

Added 'watchlist' tag to look out for further cases.
Created: 5 Nov 2018, 9:25 a.m.

Alice Gardham (Genomics England)

Green List (high evidence)

Comment when marking as ready: Offered on GOSH PCH gene panel. Recognised on G2P
Created: 14 Nov 2016, 11:27 a.m.
Offered on GOSH PCH gene panel as cerebellar hypoplasia is a recognised feature
Created: 14 Nov 2016, 11:26 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polymicrogyria with optic nerve hypoplasia, 613180

Publications

History Filter Activity

5 Nov 2018, Gel status: 2

Added Tag

Rebecca Foulger (Genomics England curator)

Tag watchlist tag was added to gene: TUBA8.

5 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).

22 Feb 2017, Gel status: 4

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

22/02/2017: Panel revised after internal clinical review and further curation.

14 Nov 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

14 Nov 2016, Gel status: 4

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Green List (High Evidence).

14 Nov 2016, Gel status: 0

Created

Alice Gardham (Genomics England)

TUBA8 was created by agardham

14 Nov 2016, Gel status: 2

Added New Source

Alice Gardham (Genomics England)

TUBA8 was added to Cerebellar hypoplasiapanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Literature