Ataxia and cerebellar anomalies - narrow panelGene: 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.
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
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
Spinocerebellar ataxia, autosomal recessive 15, MIM#615705
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: RUBCN were set to PMID: 20826435
Gene: rubcn has been classified as Red List (Low Evidence).
Tag founder-effect tag was added to gene: RUBCN.
Phenotypes for gene: RUBCN were changed from to Spinocerebellar ataxia, autosomal recessive 15, OMIM:615705
Rebecca Foulger: Comment on list classification
gene: RUBCN was added gene: RUBCN was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Red Mode of inheritance for gene: RUBCN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RUBCN were set to PMID: 20826435