Early onset or syndromic epilepsy

Gene: TAF8

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 9:39 a.m. | Last Modified: 1 Feb 2023, 9:39 a.m.

Panel Version: 3.29

Comment on list classification: New gene added by Jana Jezkova. There is sufficient evidence to promote this gene to Green at the next GMS panel update.

TAF8 is associated with a relevant phenotype in OMIM (MIM# 619972) but is not yet listed in G2P.

8 individuals from 5 families have been reported in literature (PMIDs: 29648665; 35759269). Four families from different ethnic backgrounds harboured the same c.781-1G>A homozygous variant while sequencing in a sib pair revealed different compound het splice variants (c.45+4A>G and c.489G>A) in the TAF8 gene. Patients presented with an overlapping phenotype including microcephaly (8/8), DD and ID (8/8), spasticity (7/8), and seizures (6/8). Brain MRI have shown hypoplastic corpus callosum, hypomyelination, enlarged ventricles in most subjects, and additionally generalised brain atrophy in two sibs.

Created: 9 Aug 2022, 3:23 p.m. | Last Modified: 9 Aug 2022, 3:23 p.m.

Panel Version: 3.1656

I don't know

Eight patients reported in total. Six patients are homozygous for a recurrent NM_138572.2, c.781-1G>A variant. In two sibling patients, two novel compound heterozygous TAF8 splice site mutations, c.45+4A > G and c.489G>A were identified, which cause aberrant splicing as well as reduced expression and mislocalization of TAF8.
Sources: Literature

Created: 26 Jul 2022, 9:56 a.m. | Last Modified: 26 Jul 2022, 9:59 a.m.

Panel Version: 3.1632

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
severe developmental delay; feeding problems; microcephaly; growth retardation; spasticity; epilepsy

Publications

• PMID: 35759269