Cerebellar hypoplasia
Gene: TUBA8Comment 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.
Comment when marking as ready: Offered on GOSH PCH gene panel. Recognised on G2PCreated: 14 Nov 2016, 11:27 a.m.
Offered on GOSH PCH gene panel as cerebellar hypoplasia is a recognised featureCreated: 14 Nov 2016, 11:26 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Polymicrogyria with optic nerve hypoplasia, 613180
Publications
Tag watchlist tag was added to gene: TUBA8.
Gene: tuba8 has been classified as Amber List (Moderate Evidence).
22/02/2017: Panel revised after internal clinical review and further curation.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
TUBA8 was created by agardham
TUBA8 was added to Cerebellar hypoplasiapanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Literature