Frequency and distribution of polyQ disease intermediate-length repeat alleles in healthy Italian population

Alessia Mongelli, Stefania Magri, Elena Salvatore, Elena Rizzo, Anna De Rosa, Tommasina Fico, Marta Gatti, Cinzia Gellera, Franco Taroni, Caterina Mariotti, Lorenzo Nanetti

Research output: Contribution to journalArticlepeer-review


Background: Huntington disease (HD) and spinocerebellar ataxia type 1-2-17 (SCA1-2-17) are adult-onset autosomal dominant diseases, caused by triplet repeat expansions in the HTT, ATXN1, ATXN2, and TBP genes. Alleles with a repeat number just below the pathological threshold are associated with reduced penetrance and meiotic instability and are defined as intermediate alleles (IAs). Objectives: We aimed to determine the frequencies of IAs in healthy Italian subjects and to compare the proportion of the IAs with the prevalence of the respective diseases. Methods: We analyzed the triplet repeat size in HTT, ATXN1, ATXN2, and TBP genes in the DNA samples from 729 consecutive adult healthy Italian subjects. Results: IAs associated with reduced penetrance were found in ATXN2 gene (1 subject, 0.1%) and TBP gene (0.82%). IAs at risk for meiotic instability were found in HTT (5.3%) and ATXN2 genes (2.7%). In ATXN1, we found a low percentage of IAs (0.4%). Alleles lacking the common CAT interruption within the CAG sequence were also rare (0.3%). Conclusions: The high frequencies of IAs in HTT and ATXN2 genes suggest a correlation with the prevalence of the diseases in our population and support the hypothesis that IAs could represent a reservoir of new pathological expansions. On the opposite, ATXN1-IA were very rare in respect to the prevalence of SCA1 in our country, and TBP- IA were more frequent than expected, suggesting that other mechanisms could influence the occurrence of novel pathological expansions.

Original languageEnglish
Pages (from-to)1475-1482
Number of pages8
JournalNeurological Sciences
Issue number6
Publication statusPublished - Jun 1 2020


  • Huntington disease
  • Intermediate alleles
  • Spinocerebellar ataxia

ASJC Scopus subject areas

  • Dermatology
  • Clinical Neurology
  • Psychiatry and Mental health


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