Ataxia and cerebellar anomalies - narrow panel

Gene: HEATR5B

Green List (high evidence)

Comment on list classification: There are three unrelated cases (2 published, 1 NHS-diagnosed) with pontocerebellar hypoplasia due to biallelic LOF variants in this gene. Tagging for expert review to gain GMS approval for including the unpublished case as evidence to promote this gene to Green.

Created: 17 Oct 2025, 2:12 p.m. | Last Modified: 17 Oct 2025, 2:17 p.m.

Panel Version: 8.25

We have received confirmation of an unpublished NHS-diagnosed family identified via R14, with three affected individuals presenting with pontocerebellar hypoplasia. The variant, present in a homozygous state in the affected individuals, had a splicing impact and confirmed out-of-frame skipping of exon 30.

Created: 17 Oct 2025, 2:07 p.m. | Last Modified: 17 Oct 2025, 2:07 p.m.

Panel Version: 8.24

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.

Created: 14 Jul 2021, 1:40 p.m. | Last Modified: 14 Jul 2021, 1:40 p.m.

Panel Version: 3.1188

I don't know

Four affected children from two families presenting with pontocerebellar hypoplasiawith neonatal seizures, severe ID and motor delay. Two homozygous splice variants were reported (c.5051–1G>A and c.5050+4A>G) in intron 31 of HEATR5B gene. Aberrant splicing was found in patient fibroblasts, which correlated with reduced levels of HEATR5B protein. Homozygous knockout mice were not viable
Sources: Literature

Created: 9 Jul 2021, 5:12 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
pontocerebellar hypoplasia; intellectual disability; seizures

Publications

• 33824466