Spinocerebellar ataxia type 3 in Israel: phenotype and genotype of a Jew Yemenite subpopulation

J Neurol. 2016 Nov;263(11):2207-2214. doi: 10.1007/s00415-016-8251-8. Epub 2016 Aug 8.


Spinocerebellar ataxia type 3 is an autosomal dominant ataxia with various phenotypes affecting Jews of Yemenite origin in Israel. Clinical and family pedigrees data of 125 Yemenite Jewish patients were collected in our clinic. All examined patients underwent a detailed neurological and bedside vestibular examination. Cytosine-adenine-guanine repeats size in the Ataxin-3 gene was measured, and patients with expanded cytosine-adenine-guanine repeats >44 were diagnosed genetically as having spinocerebellar ataxia type 3. We estimated a disease prevalence rate of about 29/100,000 in Jew of Yemenite descendents living in Israel. We were able to group patients into 17 families. Mean age of onset was 44 years. 74 % of our population expressed neurological signs compatible with sub-phenotype III, i.e., ataxia and polyneuropathy. Vestibulo-ocular reflex deficit detected on bedside examination was found in 90 % of the patients. The mean number of cytosine-adenine-guanine repeats in the Ataxin-3 gene of the diseased allele was 67 (range 55-76). Age of onset was inversely correlated with the number of cytosine-adenine-guanine repeats (r = -0.7) and was significantly earlier among male patients. Though the mean number of cytosine-adenine-guanine repeats was not larger in the offspring, their age of onset was significantly earlier than that of their parents. In addition, paternal offspring expressed the disease significantly earlier than maternal offspring. Signs and stages of disease seem to progress slower during the first 10-15 years of the disease and faster afterward. A high disease prevalence rate in our Yemenite Jewish subpopulation is similar to that found in other isolated populations in other countries. Vestibulo-ocular reflex deficit detected on bedside examination should be added as part of the phenotype of Yemenite Jewish patients. Our clinical and genetic findings are in partial agreement with other spinocerebellar ataxia type 3 population studies and are relevant to patient management and the design of further studies.

Keywords: Genotype; Jew Yemenite; Phenotype; Spinocerebellar ataxia; Vestibulo-ocular reflex.

MeSH terms

  • Adult
  • Age of Onset
  • DNA Mutational Analysis
  • Female
  • Genotype
  • Humans
  • Jews* / genetics
  • Machado-Joseph Disease / epidemiology
  • Machado-Joseph Disease / genetics*
  • Machado-Joseph Disease / physiopathology*
  • Male
  • Middle Aged
  • Phenotype
  • ROC Curve
  • Retrospective Studies
  • Severity of Illness Index
  • Trinucleotide Repeats / genetics*
  • Yemen / epidemiology
  • Yemen / ethnology