Malformations of cortical developmentGene: TUBA8
Comment on list classification: Demoted from Green to Amber based on re-review of evidence. Demotion was 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:
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, 9:22 a.m.
Comment on mode of inheritance: Biallelic MOI supported by OMIM and DD-Gene2Phenotype.
Created: 5 Nov 2018, 9:20 a.m.
Comment when marking as ready: Recognised on G2P
Created: 19 Dec 2016, 10:30 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
Tag watchlist tag was added to gene: TUBA8.
Gene: tuba8 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: TUBA8 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
Phenotypes for TUBA8 were set to Polymicrogyria with optic nerve hypoplasia 613180
Publications for TUBA8 were set to 19896110
TUBA8 was added to Malformations of cortical developmentpanel. Sources: UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
Promoted to Version 1 on 22nd November 2016
TUBA8 was added to Malformations of cortical developmentpanel. Sources: UKGTN
TUBA8 was created by sleigh