Genetic Biomarkers in Aortopathy

Abstract

The field of aortopathy, in common with other genomic disorders, is undergoing a revolution. This is largely driven by the implementation of newer forms of genetic sequencing (massively parallel or next-generation sequencing). Advantages conferred by this technology include reduced costs, reduced sequencing time and the ability to simultaneously test multiple genes. This has a significant advantage in the identification of genes disrupted in heritable aortopathies. These advances are enabling scientists and clinicians to identify key molecular pathways; translating fundamental genetic findings into a better understanding of disease mechanisms is ultimately leading to effective treatments. In outlining contemporary knowledge of genetic biomarkers in aortopathy we seek to demonstrate that the era of genomically orientated decision-making is here.

KEYWORDS::

• aortopathy
• FBN1
• heritable
• Loeys–Dietz syndrome
• Marfan syndrome
• TGF-β

Financial & competing interests disclosure

G Rea is currently working at Royal Brompton Hospital as a Clinical Research Fellow and is receiving British Heart Foundation funding for her work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of the manuscript.

Notes

† Caveat: without discriminating features of Shprintzen–Goldberg syndrome, Loeys–Dietz syndrome or vascular Ehlers–Danlos syndrome (as defined elsewhere) and after TGFBR1/2, collagen biochemistry AND COL3A1 testing if indicated. Other conditions/genes will emerge with time.

Ao: Aortic diameter at the sinuses of Valsalva above indicated Z-score or aortic root dissection; EL: Ectopialentis; ELS: Ectopialentis syndrome;FBN1: FBN1 mutation (as defined inBox 3); FBN1 not known with Ao, FBN1 mutation that has not previously been associated aortic root aneurysm/dissection; FBN1 with known Ao, FBN1 mutation that has been identified in an individual with aortic aneurysm; MASS: Myopia, mitral valve prolapse, borderline (Z <2) aortic root dilatation, striae, skeletal findings phenotype; MFS: Marfan syndrome; MVPS: Mitral valve prolapse; MVPS: Mitral valve prolapse syndrome; Pt: Point; Syst: Systemic score(Box 2); Z: Z-score.

Reproduced with permission from BMJ Publishing Group Ltd [28].

Reproduced with permission from BMJ Publishing Group Ltd [28].

In the EGF consensus sequence, m and n represent variable numbers of residues.

Reproduced with permission from BMJ Publishing Group Ltd [28].

Additional information

Funding

G Rea is currently working at Royal Brompton Hospital as a Clinical Research Fellow and is receiving British Heart Foundation funding for her work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.