Atmaja, Dian Mayasari Aji and Pals, Gerard and Bahrudin, Bahrudin and Sistermans, Erik and Faradz, Sultana MH (2013) MUTATION ANALYSIS IN SMAD2, TGFβ2, AND SMURF2 GENES IN PATIENTS WITH THORACIC AORTIC ANEURYSM AND DISSECTION. Masters thesis, Universitas Diponegoro.

	Text (Cover) Cover.pdf Download (150kB)
	Text (Chapter 1) Chapter 1.pdf Download (61kB)
	Text (Chapter 2) Chapter 2.pdf Restricted to Registered users only Download (1MB) | Request a copy
	Text (Chapter 3) Chapter 3.pdf Restricted to Registered users only Download (105kB) | Request a copy
	Text (Chapter 4) Chapter 4.pdf Restricted to Registered users only Download (704kB) | Request a copy
	Text (Chapter 5) Chapter 5.pdf Restricted to Registered users only Download (92kB) | Request a copy
	Text (Chapter 6) Chapter 6.pdf Restricted to Registered users only Download (40kB) | Request a copy
	Text (Chapter 7) Chapter 7.pdf Restricted to Registered users only Download (57kB) | Request a copy
	Text (References) References.pdf Restricted to Registered users only Download (67kB) | Request a copy
	Text (Appendixes) Appendixes.pdf Restricted to Registered users only Download (1MB) | Request a copy

Abstract

Background: Thoracic aortic aneurysm and dissection (TAAD) is one of 15th most leading cause of the death in USA and of the silent killer in the world. Several genes associated with TAAD have been recognized, i.e. FBN1, ACTA2, TGFβR1, TGFβR2, MYH11, MYLK and SMAD3. However, many cases of familial
TAAD have not been found for the mutation in those genes. The other genes that might be had association with TAAD are SMAD2, TGFβ2 and SMURF2.

Methods: Three hundred sixty five patients with TAAD and related disorders, who did not carry any mutation in FBN1, TGFβR1, TGFβR2, ACTA2 and MYH11 were included. Mutation screening of the gene variants in SMAD2, TGFβ2 and SMURF2 were done by using high resolution melting (HRM) technique. The aberrant sample patterns on the curve analysis then were sequenced. Confirmation of the mutation was done by comparing the HRM curves between patients and the healthy control. The pathogenicity potency of the mutation was predicted by using mutation prediction software SIFT and align GVGD, which integrated in Alamut software. Phosphorylation/glycosylation site was predicted by YinOYang
software.

Results: Three patients were found to carry SMAD2 mutation, i.e., c.6_8del, c.1346T>C, c.1369G>A. One mutation, c.1369G>A was predicted to increase phosphorylation, and the other mutations predicted to loss of phosphorylation/glycosylation site. All of the SMAD2 mutations were not found in the control. One patient was found to carry nonsense mutation of TGFβ2,
c.547C>T (Gln183X). Two missense mutation of TGFβ2, c.272G>A and c.703C>G were found in four patients and have been registered in SNP databases with frequency less than 1%. All mutations in SMAD2 and TGFβ2 were predicted to be pathogenic. No mutation was found in SMURF2 gene.

Conclusion: Three novel mutations were found in SMAD2 gene and one novel mutation was found in TGFβ2 in TAAD patients who did not carry any mutation in FBN1, TGFβR1, TGFβR2, ACTA2 and MYH11.

Keywords: Thoracic aortic aneurysm and dissection, mutation, SMAD2, TGFβ2, SMURF2

Actions (login required)

View Item