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@ARTICLE{Gardiner:140801,
author = {Gardiner, Sarah L and Boogaard, Merel W and Trompet, Stella
and de Mutsert, Renée and Rosendaal, Frits R and Gussekloo,
Jacobijn and Jukema, J Wouter and Roos, Raymund A C and
Aziz, Ahmad},
title = {{P}revalence of {C}arriers of {I}ntermediate and
{P}athological {P}olyglutamine {D}isease-{A}ssociated
{A}lleles {A}mong {L}arge {P}opulation-{B}ased {C}ohorts.},
journal = {JAMA neurology},
volume = {76},
number = {6},
issn = {2168-6149},
address = {Chicago, Ill.},
publisher = {American Medical Association},
reportid = {DZNE-2020-07123},
pages = {650},
year = {2019},
abstract = {Nine hereditary neurodegenerative diseases are known as
polyglutamine diseases, including Huntington disease, 6
spinocerebellar ataxias (SCAs) (SCA1, SCA2, SCA3, SCA6,
SCA7, and SCA17), dentatorubral-pallidoluysion atrophy, and
spinal bulbar muscular atrophy.To determine the prevalence
of carriers of intermediate and pathological polyglutamine
disease-associated alleles among the general population.This
observational cross-sectional study included data from 5
large European population-based cohorts that were compiled
between 1997 and 2012, and the analyses were conducted in
2018. In total, 16 547 DNA samples were obtained from
participants of the 5 cohorts. Individuals with a lifetime
diagnosis of major depression were excluded (n = 2351).
In the remaining 14 196 participants without an
established polyglutamine disease diagnosis, the CAG repeat
size in both alleles of all 9 polyglutamine
disease-associated genes (PDAGs) (ie, ATXN1, ATXN2, ATXN3,
CACNA1A, ATXN7, TBP, HTT, ATN1, and AR) was determined.The
number of CAG repeats in the alleles of the 9 PDAGs.The
number of individuals with alleles within the intermediate
or pathological range per PDAG, as well as differences in
sex, age, and body mass index between individuals carrying
alleles within the normal or intermediate range and
individuals carrying alleles within the pathological range
of PDAGs.In the 14 196 analyzed participants (age range,
18-99 years; $56.3\%$ female), $10.7\%$ had a CAG repeat
number within the intermediate range of at least 1 PDAG.
Moreover, up to $1.3\%$ of the participants had a CAG repeat
number within the disease-causing range, predominantly in
the lower pathological range associated with elderly onset.
No differences in sex, age, or body mass index were found
between individuals with CAG repeat numbers within the
pathological range and individuals with CAG repeat numbers
within the normal or intermediate range.These results
indicate a high prevalence of individuals carrying
intermediate and pathological ranges of polyglutamine
disease-associated alleles among the general population.
Therefore, a substantially larger proportion of individuals
than previously estimated may be at risk of developing a
polyglutamine disease later in life or bearing children with
a de novo mutation.},
cin = {AG Breteler 1},
ddc = {610},
cid = {I:(DE-2719)1012001},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30933216},
pmc = {pmc:PMC6563569},
doi = {10.1001/jamaneurol.2019.0423},
url = {https://pub.dzne.de/record/140801},
}