Ataxia and cerebellar anomalies - narrow panel

Gene: RUBCN

Comment on list classification: Gene was reassessed following a Green review by Zornitza Stark. Five individuals from two consanguineous Saudi families have been identified (PMID: 20826435; 32450808) who presented with early-onset ataxia, dysarthria, and developmental delay. All harboured the same c.2624delC variant, which was confirmed to be a founder variant by autozygosity mapping. Limited functional data showing the variant results in mislocalisation of the mutant protein from the late endosome and lysosomes to diffuse cytosolic distribution.

*Note the third publication identified by Zornitza (PMID:30237576) refers to the same sib pair as in PMID:32450808. The variants appeared distinct as the two papers refer to different reference sequences (NM_014687 vs NM_001145642.2) but the variant/case are in fact the same.
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Overall as there is only a single variant in a single population with only limited in vitro functional support, maintaining Red rating on this panel until further evidence on the gene/variants emerges.

Created: 16 Jun 2021, 3:51 p.m. | Last Modified: 16 Jun 2021, 3:51 p.m.

Panel Version: 2.200

Green List (high evidence)

Three consanguineous families reported in the literature with homozygous truncating variants in this gene and ataxia. Two have the same founder variant. Supportive in vitro assays.

Created: 12 Sep 2020, 7:43 a.m. | Last Modified: 12 Sep 2020, 7:43 a.m.

Panel Version: 2.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spinocerebellar ataxia, autosomal recessive 15, MIM#615705

Publications

• 20826435
• 30237576
• 32450808

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