TY - JOUR
T1 - Frequency and distribution of polyQ disease intermediate-length repeat alleles in healthy Italian population
AU - Mongelli, Alessia
AU - Magri, Stefania
AU - Salvatore, Elena
AU - Rizzo, Elena
AU - De Rosa, Anna
AU - Fico, Tommasina
AU - Gatti, Marta
AU - Gellera, Cinzia
AU - Taroni, Franco
AU - Mariotti, Caterina
AU - Nanetti, Lorenzo
N1 - Funding Information:
The study was supported by the Italian Ministry of Health (Grant GR-2013-02357821 to LN).
Publisher Copyright:
© 2020, Fondazione Società Italiana di Neurologia.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - Huntington disease
KW - Intermediate alleles
KW - Spinocerebellar ataxia
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U2 - 10.1007/s10072-019-04233-3
DO - 10.1007/s10072-019-04233-3
M3 - Article
C2 - 31940111
AN - SCOPUS:85078630562
VL - 41
SP - 1475
EP - 1482
JO - Neurological Sciences
JF - Neurological Sciences
SN - 1590-1874
IS - 6
ER -