Spinocerebellar Ataxia Type 10 with Atypical Clinical Manifestation in Han Chinese

Cerebellum. 2023 Jun;22(3):355-362. doi: 10.1007/s12311-022-01405-4. Epub 2022 Apr 19.

Abstract

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant cerebellar ataxia accompanied by extracerebellar signs and other neurological disorders. It is caused by an expansion of the ATTCT pentanucleotide repeat in intron 9 of ATXN10. Cases of SCA10, formerly confined to America, have been reported in Europe and Asia. In the present study, we aim to report an atypical SCA10 family in China and provide a reference for the diagnosis of SCA10 in Asia by comparing their clinical and genetic features with former SCA10 pedigrees. Genomic DNA was extracted from patients and subjected to RP-PCR (repeat-primed PCR), Southern blotting, and haplotype analysis to determine the genetic pathogenesis. Patients with SCA10 in this pedigree demonstrated atypical SCA10 manifestations, including the absence of seizures and ocular abnormalities. Magnetic resonance imaging (MRI) showed cerebellar atrophy in five patients with available data. RP-PCR and Southern blotting revealed abnormal expansion. Analysis of single nucleotide polymorphisms (SNPs) surrounding the SCA10 locus in the proband and other affected family members revealed the "C-expansion-G-G-C" haplotype, consistent with former studies. These findings imply that the SCA10 mutation may have occurred before the Amerindian migration from East Asia to North America. It also suggested that SCA10 should be taken into account during differential diagnosis in patients of Asian ancestry, even if they do not present with typical features such as epilepsy.

Keywords: ATXN10; Atypical clinical manifestation; Genetic analysis; SCA.

MeSH terms

  • DNA Repeat Expansion
  • East Asian People*
  • Humans
  • Mutation
  • Spinocerebellar Ataxias* / genetics

Supplementary concepts

  • Spinocerebellar Ataxia 10