To identify disease-causing gene mutations in a Dutch cohort of PSC patients who were diagnosed before the age of 13.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Identification of rare coding variants of large effect that predict early-onset
PSC
Secondary outcome
Not applicable
Background summary
Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown
etiology leading to fibrotic destruction of the bile ducts and ultimately to
the need for liver transplantation (LTx) in young adults. When PSC develops
before the age of 13 it is always associated with inflammatory bowel disease
(IBD), and genetics play an important role in predisposing children to
early-onset PSC. Though several PSC susceptible genes and variants have been
identified, large part of the heritability for PSC is still unexplained. We aim
to screen the exonic regions of all the genes in patients with early-onset PSC
using whole-exome sequencing (WES) to discover novel PSC related variants and
genes.
Study objective
To identify disease-causing gene mutations in a Dutch cohort of PSC patients
who were diagnosed before the age of 13.
Study design
Multicenter case-control study in several Dutch hospitals with sample
collection between August 2016 and July 2017.
Study burden and risks
For patients with early-onset PSC the physical discomfort associated with
participation is negligible, as they will undergo routine venepunctures at
regular health checks. For this study two extra tubes (2 x 10 ml) will be
drawn. The healthy relatives will need to undergo one venepuncture, which would
otherwise not have taken place. WES will undoubtedly solve diagnostic dilemmas;
however, incidental findings (IF) that may have medical and social implications
will also be discovered. Actionable IF will be disclosed to participants,
unless they have opted-out on the pre-test informed consent form.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
This study involves two groups of participants:
(1) An affected individual who developed PSC before the age of 13, and in whom PSC was confirmed with either cholangiography or liver biopsy
(2) Parents of participants of group 1 ;Eligible candidates of group 1 can have any age.
Confirmation of PSC by imaging is defined as the presence of multifocal strictures, focal dilatation, or beading of the biliary tree. Histological confirmation is defined as the presence of bile duct damage, onion-skinned peri-ductal fibrosis, inflammation, portal edema or fibrosis, ductopenia, ductular proliferation, or cholestasis
Exclusion criteria
Patients with PSC due to secondary causes such as surgery, trauma, cancer or infection will be excluded from participation in this study
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 | NL57806.042.16 |