To include Dutch subjects in a Canadian study to establish the frequency of intergenerational CAG size changes for individuals with an intermediate allele (27-35 CAG) for Huntington disease. This will allow us to understand the evolution of HD…
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To establish the frequency that an intermediate allele (27-35 CAG) will expand
into the HD range (>35 CAG) during transmission to the next generation.
Secondary outcome
Secondary study parameters may include factors known to influence the
likelihood of repeat instability such as parental age, family history, and HD
haplotype if applicable.
Background summary
Direct mutation analysis for Huntington disease (HD) became possible in 1993
with the identification of an expanded CAG trinucleotide repeat within the HD
gene as the mutation underlying the disease. Expansion of CAG length beyond 35
repeats is associated with the clinical presentation of HD. Intermediate
alleles for HD are defined as being below the affected CAG range but have the
potential to expand to >35 CAG repeats within one generation. Therefore,
intermediate allele carriers are not at risk to develop HD themselves, but due
to CAG trinucleotide repeat instability, their offspring are at risk of
inheriting an expanded allele with a CAG size in the disease-associated range.
The current CAG range for intermediate alleles is between 27 and 35 repeats.
Risk figures that quantify the likelihood that an intermediate allele will
expand into the HD range when passed to the next generation would be valuable
for clinical services. Intermediate allele carriers require accurate risk
estimates in which to base their reproductive decision-making on. Further, it
is essential that we consider the magnitude and frequency of intermediate
allele expansion when developing clinical standards of care. Determining
accurate risk estimates for inclusion in policy is vital in order to provide
accurate and standardized care. Only one study to date has published risk
estimates for intermediate allele repeat expansion into the HD range. However
these risk estimates are extremely limited due to the use of an exceedingly
small sample size and failure to account for the influence of CAG size on
repeat instability. Given these limitations they are not suitable for use in
clinical practice. This will be the first study to establish CAG size-specific
frequencies of intermediate allele repeat expansion into the HD range for use
in health services.
The allele frequency of intermediate CAG repeats in the HTT gene in the
Netherlands is high (high background risk). Adding known carriers from our
patient population to the Canadian study would imply a substantial increase of
eligible subjects.
Study objective
To include Dutch subjects in a Canadian study to establish the frequency of
intergenerational CAG size changes for individuals with an intermediate allele
(27-35 CAG) for Huntington disease. This will allow us to understand the
evolution of HD chromosomes and the origins of new mutations for HD.
Study design
Observational study.
Study burden and risks
There are no known risks to participating in this study. Some participants may
feel awkward or embarrassed about collecting the sample. A questionnaire will
be completed.
Postbus 9600
2300 RC Leiden
NL
Postbus 9600
2300 RC Leiden
NL
Listed location countries
Age
Inclusion criteria
Males with an intermediate CAG repeat in the Huntington gene.
Exclusion criteria
Azoospermia.
Vasectomy.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL28243.000.09 |