Childhood onset hereditary spastic paraplegia

Gene: RNASEH2B

The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.

Created: 14 Mar 2022, 1:30 p.m. | Last Modified: 14 Mar 2022, 1:30 p.m.

Panel Version: 2.130

Comment on list classification: Sufficient evidence of childhood-onset spasticity associated with variants in this gene. Upgraded from Red to Amber but should be promoted to Green at the next GMS panel update.

Created: 29 Nov 2021, 4:02 p.m. | Last Modified: 29 Nov 2021, 4:02 p.m.

Panel Version: 2.120

Green List (high evidence)

Spasticity commonly described in AGS2, in some cases as the predominant presenting feature.

Created: 20 Sep 2020, 6:37 a.m. | Last Modified: 20 Sep 2020, 6:37 a.m.

Panel Version: 2.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Aicardi-Goutieres syndrome 2, MIM# 610181

Publications

• 29691679
• 30223285
• 29239743
• 28762473

Variants in this GENE are reported as part of current diagnostic practice

Comment on list classification: New Green rated gene added by reviewer after panel sign off to V1.0- to be reviewed at next panel update with the Neurology Test Group for GMS. The 100,000 Genomes Project has identified one case and recent publications have reported RNASEH2B variants in homozygous status in patients with spastic paraplegia. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.

Created: 12 Nov 2019, 1:11 p.m. | Last Modified: 12 Nov 2019, 1:11 p.m.

Panel Version: 2.2

Green List (high evidence)

Above publications report the association of pure, childhood-onset spastic paraparesis in association with missense recessive variants in RNASEH2B.
Sources: Other

Created: 12 Nov 2019, 12:47 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
hereditary spastic paraparesis

Publications

• PMID:30223285, PMID:25243380, PMID:29691679 and PMID:28762473

Mode of pathogenicity
Other