Fetal anomalies
Gene: TUBA8The 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
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
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
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 HYPOPLASIACreated: 11 Dec 2018, 9:05 a.m.
Gene: tuba8 has been classified as Amber List (Moderate Evidence).
Tag for-review was removed from gene: TUBA8.
Gene: tuba8 has been classified as Green List (High Evidence).
Gene: tuba8 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: TUBA8 were changed from POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA to POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA; Cortical dysplasia, complex, with other brain malformations 8, 613180
Publications for gene: TUBA8 were set to
Tag for-review tag was added to gene: TUBA8.
gene: TUBA8 was added gene: TUBA8 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: TUBA8 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TUBA8 were set to POLYMICROGYRIA WITH OPTIC NERVE HYPOPLASIA