Spinocerebellar ataxia type 48: last but not least: Neurological Sciences

G. De Michele, D. Galatolo, M. Barghigiani, D. Dello Iacovo, R. Trovato, A. Tessa, E. Salvatore, A. Filla, F.M. Santorelli

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Biallelic mutations in STUB1, which encodes the E3 ubiquitin ligase CHIP, were originally described in association with SCAR16, a rare autosomal recessive spinocerebellar ataxia, so far reported in 16 kindreds. In the last 2 years, a new form of spinocerebellar ataxia (SCA48), associated with heterozygous mutations in the same gene, has been described in 12 kindreds with autosomal dominant inheritance. Methods: We reviewed molecular and clinical findings of both SCAR16 and SCA48 described patients. Results and conclusion: SCAR16 is characterized by early onset spastic ataxia and a wide disease spectrum, including cognitive dysfunction, hyperkinetic disorders, epilepsy, peripheral neuropathy, and hypogonadism. SCA48 is an adult-onset syndrome characterized by ataxia and cognitive-psychiatric features, variably associated with chorea, parkinsonism, dystonia, and urinary symptoms. SCA48, the last dominant ataxia to be described, could emerge as the most frequent among the SCAs due to conventional mutations. The overlap of several clinical signs between SCAR16 and SCA48 indicates the presence of a continuous clinical spectrum among recessively and dominantly inherited mutations of STUB1. Different kinds of mutations, scattered over the three gene domains, have been found in both disorders. Their pathogenesis and the relationship between SCA48 and SCAR16 remain to be clarified. © 2020, Fondazione Società Italiana di Neurologia.
Original languageEnglish
Pages (from-to)2423-2432
Number of pages10
JournalNeurol. Sci.
Volume41
Issue number9
DOIs
Publication statusPublished - 2020

Keywords

  • Ataxia
  • Cognitive impairment
  • NGS
  • SCA48
  • SCAR16
  • STUB1
  • chaperone
  • chip protein
  • unclassified drug
  • autosomal dominant inheritance
  • clinical feature
  • cognitive defect
  • gene
  • gene mutation
  • hereditary ataxia
  • heterozygote
  • human
  • inheritance
  • nonhuman
  • pathogenesis
  • penetrance
  • phenotype
  • prevalence
  • protein function
  • Review
  • spinocerebellar ataxia type 16
  • spinocerebellar ataxia type 17
  • spinocerebellar ataxia type 48
  • stub1 gene

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