Abstract

Background Spinocerebellar ataxias comprise a group of neurodegenerative disorders characterized by progressive cerebellar ataxia with clinical and genetic heterogeneity. Autosomal recessive spinocerebellar ataxia type 16 (SCAR16) is characterized by cerebellar ataxia accompanied by pyramidal tract damage, cognitive decline, hypogonadism, and extrapyramidal symptoms. SCAR16 is caused by mutations in the STIP1 homology and U-box containing protein 1 ( STUB1 ) gene. Methods The whole-exome sequencing combined with long-range flanking polymerase chain reaction (PCR) were performed in a Chinese SCAR16 patient. Furthermore, we used quantitative real-time PCR and western blot analysis to investigate the function of variant in STUB1 in cultured cells. Results We identified a compound heterozygote in STUB1 containing a novel nonsense variant, NM_005861.4:c.352 C > T, p.(Gln118*), and a pathogenic missense variant, NM_005861.4:c.433 A > C, p.(Lys145Gln), in a Chinese SCAR16 patient. The age at onset was 27 years old with clinical characteristics of cerebellar ataxia and increased tendon reflex. We found that STUB1 p.(Gln118*) variant generated truncated proteins of the C-terminus of Hsc70-interacting protein and caused the loss function of ubiquitin ligase activity. Conclusions Our results confirmed the pathogenicity of the STUB1 p.(Gln118*) variant, expanding the spectrum of causative variants associated with SCAR16.