Ataxia and cerebellar anomalies - narrow panel

Gene: SVBP

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). SVBP is associated with a relevant phenotype in OMIM. 12 individuals from 5 independent families (PMIDs: 31363758 and 30607023) reported at present with biallelic variants.

Rating Amber as phenotypes include ataxia in only 2 families (remaining cases present spasticity rather than ataxia).

Created: 4 Dec 2020, 1:03 p.m. | Last Modified: 4 Dec 2020, 1:03 p.m.

Panel Version: 2.33

Green List (high evidence)

5 families with homozygous mutations in SVBP; syndromic cause of paediatric ataxia. Some shared same founder variant, p.Q28*. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls.
Sources: Expert list

Created: 13 Sep 2020, 6:58 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, OMIM #618569

Publications

• 31363758
• 30607023

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