Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome

Study Overview
=================
Brief Summary
-----------------
The study aim is: To examine aortic tissue by light microscopy To examine aortic tissue by electron microscopy To study changes in the epigenome and transcriptome of the X chromosome specific to aortic tissue. To examine aortic tissue using biochemistry including proteomics. 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.

Official Title
-----------------
Aortopathy in Persons With Bicuspid Aortic Valve, Turner and Marfan Syndrome

Conditions
-----------------
Turner Syndrome, Bicuspid Aortic Valve, Marfan Syndrome

Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Turner syndrome (TS)<br>TS verified by genotyping Age > 18 years awaiting operation due to aortic dilation | |
| Marfan syndrome (MS)<br>Females with MS verified clinically or by genotyping Age > 18 years awaiting operation due to aortic dilation | |
| Bicuspid aortic valve<br>females with bicuspid aortic valve Age > 18 years awaiting operation due to aortic dilation | |
| Controls<br>Men/females who died from conditions other than aortic dilation or dissection. Age 20-60 years. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histone modifications | Permissive and repressive histone modifications on the X-chromosome | Cross sectional | 
| mRNA and non-coding RNAs | Identification of the entire transcriptome including both mRNA and non-coding RNAs (lincRNA as well as miRNA)from the X-chromosome | Cross sectional | 
| DNA-methylations of CpG-islands | mapping DNA-methylations of CpG-islands | Cross sectional | 
| Electron microscopic evaluation |  | Cross sectional | 
| Karyotyping by FISH and conventional karyotyping |  | Cross sectional | 
| Proteomics |  | Cross sectional | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sex chromosome, Turner Syndrome, Marfan syndrome, Bicuspid aortic valve, Aortic Aneurysm, Epigenetics, Transcriptome, non-coding RNA, Electron microscopy, Proteomics