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

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).

Study Overview

• Status: Completed
• Conditions: Marfan Syndrome; Bicuspid Aortic Valve; Turner Syndrome

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.

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• Denmark
  • Aarhus C, Denmark, 8000
    • Department of Endocrinology and Internal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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).

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Turner syndrome (TS); TS verified by genotyping Age > 18 years awaiting operation due to aortic dilation
Marfan syndrome (MS); Females with MS verified clinically or by genotyping Age > 18 years awaiting operation due to aortic dilation
Bicuspid aortic valve; females with bicuspid aortic valve Age > 18 years awaiting operation due to aortic dilation
Controls; 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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Christian Trolle, Aarhus University Hospital; Study Director: Claus H Gravholt, MD, Ph.d., Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: January 2, 2013
• First Submitted That Met QC Criteria: January 2, 2013
• First Posted (Estimate): January 4, 2013

Study Record Updates

• Last Update Posted (Estimate): May 24, 2016
• Last Update Submitted That Met QC Criteria: May 23, 2016
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Marfan syndrome; Bicuspid aortic valve; Proteomics; Turner Syndrome; Epigenetics; Aortic Aneurysm; non-coding RNA; Sex chromosome; Transcriptome; Electron microscopy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Disease; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Aortic Valve Disease; Bone Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Chromosome Disorders; Bone Diseases, Developmental; Sex Chromosome Disorders; Limb Deformities, Congenital; Sex Chromosome Disorders of Sex Development; Syndrome; Heart Valve Diseases; Marfan Syndrome; Arachnodactyly; Bicuspid Aortic Valve Disease; Turner Syndrome; Gonadal Dysgenesis
• Other Study ID Numbers: 1-10-72-561-12