Clinical trial NCT01760668: Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome
Official title: Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Turner Syndrome
Bicuspid Aortic Valve
Marfan Syndrome
Keywords: Sex chromosome
Turner Syndrome
Marfan syndrome
Bicuspid aortic valve
Aortic Aneurysm
Epigenetics
Transcriptome
non-coding RNA
Electron microscopy
Proteomics
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2013-01-04
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with Turner syndrome will be recruited from out-patient clinics. Individuals with Turner syndrome, Marfan syndrome and bicuspid aortic valve will be recruited from departments of cardiology or thoracic surgery in Odense, Copenhagen or Aarhus (Denmark).

Brief summary: The study aim is:

1. To examine aortic tissue by light microscopy
2. To examine aortic tissue by electron microscopy
3. To study changes in the epigenome and transcriptome of the X chromosome specific to aortic tissue.
4. To examine aortic tissue using biochemistry including proteomics.
5. To establish the karyotype of fibroblasts with standard chromosome examination on 10 meta-phases as well as by fluorescent in situ hybridization (FISH) with probes covering the X and Y chromosome. Using the latter 200 meta-phases will be examined.

30 controls who did not die from aortic dissection or dilation will be recruited from The Department of Forensic Medicine at Aarhus University Hospital.

The investigators will subject samples of aortic tissue from women undergoing prophylactic aortic surgery due to either Marfan syndrome or bicuspid aortic valve to the same panel of examinations (except karyotyping). Lastly the investigators will compare the results from the three groups (Turner syndrome, Marfan syndrome and Bicuspid aortic valve).

Detailed description: Turner syndrome is a congenital complete or partial lack of one of the female sex chromosomes affecting 1 of 2000 live born girls. The syndrome is characterized by an increased prevalence of ischemic heart disease, aortic dilation and dissection, hypertension, stroke and autoimmune diseases in general.

Eligibility criteria: Turner syndrome (TS).

A. Inclusion

* TS verified by genotyping
* Age \> 18 years
* Awaiting operation due to aortic dilation

B. Exclusion - Previous aortic dissection or operation of the aorta (per-cutaneous or open surgery)

Marfan syndrome (MS)

A. Inclusion

* Females with MS verified clinically or by genotyping
* Age \> 18 years
* Awaiting operation due to aortic dilation

B. Exclusion

- Previous aortic dissection or operation of the aorta (per-cutaneous or open surgery)

Bicuspid aortic valve

A. Inclusion

* Females with Bicuspid aortic valve
* Age \> 18 years
* Awaiting operation due to aortic dilation

B. Exclusion - Previous aortic dissection or operation of the aorta (per-cutaneous or open surgery)

Controls

A. Inclusion

* Men/females who died from conditions other than aortic dilation or dissection.
* Age 20-60 years.

B. Exclusion

- Previous aortic dissection or operation of the aorta (per-cutaneous or open surgery)

Primary outcomes:
measure: Histone modifications
timeFrame: Cross sectional
measure: mRNA and non-coding RNAs
timeFrame: Cross sectional
measure: DNA-methylations of CpG-islands
timeFrame: Cross sectional
measure: Electron microscopic evaluation
timeFrame: Cross sectional
measure: Karyotyping by FISH and conventional karyotyping
timeFrame: Cross sectional
measure: Proteomics
timeFrame: Cross sectional
Secondary outcomes:
Other outcomes:
Locations:
city: Aarhus C
country: Denmark
facility: Department of Endocrinology and Internal medicine
Study officials:
affiliation: Aarhus University Hospital
name: Christian Trolle
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University Hospital
name: Claus H Gravholt, MD, Ph.d.
role: STUDY_DIRECTOR
References: