Ataxia and cerebellar anomalies - narrow panel

Gene: RNU12

Red List (low evidence)

Comment on list classification: There is one large consanguineous pedigree reported in literature, with a biallelic RNU12 mutation segregating with early-onset ataxia. RNU12 should be rated Red for Ataxia and cerebellar anomalies - narrow panel, until more evidence emerges.

Created: 19 Dec 2025, 3:50 p.m. | Last Modified: 19 Dec 2025, 3:50 p.m.

Panel Version: 8.36

PMID: 27863452 Elsaid et al., 2017
Report of a large consanguineous pedigree with 6 individuals presenting with early-onset ataxia (onset <2 yrs old). Affected individuals were homozygous for RNU12 84C>U mutation. Method: WGS confirmed by Sanger. 2 other mutations segregates with disease in a recessive manner, affecting non-coding regions of genes POLDIP3 and PACSIN2 (uncertain significance).
Affected individuals showed a significant increase in RNU12 snRNA levels; expression of POLDIP3 and PACSIN2 did not differ between affected and unaffected members.
Phenotype spectrum: truncal ataxia 6/6, abnormal cerebellum 5/5 (5 assessed), hypotonia in infancy 5/6, mild learning difficulties 4/6, seizures (febrile / complex partial) 4/6, dysarthric speech 5/6, abnormal gait & falls 5/6.

Functional evidence: PMID: 33577674 Norppa and Frilander, 2021: Show that the 84C>U mutation leads to accelerated decay of the RNU12 snRNA, resulting in significantly reduced steady-state U12 snRNA levels (cell line model).

This gene is putatively linked to Spinocerebellar ataxia, autosomal recessive 33, MIM:620208 and linked to CDAGS syndrome, MIM:603116 (OMIM accessed 19th Dec 2025).
Sources: Literature

Created: 19 Dec 2025, 3:47 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Spinocerebellar ataxia, autosomal recessive 33, OMIM:620208

Publications

• 27863452
• 33577674