Informative STR Markers for Marfan Syndrome in Birjand, Iran

Document Type: Original Article

Authors

1 Department of Human Genetics, Immunology Research Centre, Avicenna Research Institute, Mashhad University of Medical Science, Mashhad, Iran

2 Birjand Hepatitis Research Centre, Birjand University of Medical Sciences, Birjand, Iran

3 Ophthalmology Department, Vali-e-Asr Hospital, Birjand University of Medical Sciences, Iran

4 Birjand Atherosclerosis and Coronary Artery Research Centre, Birjand University of Medical Sciences, Birjand, Iran

5 Medical Genetic Research Centre (MGRC), School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s)
Marfan syndrome (MFS) is a severe connective tissue disorder withan autosomal dominant inheritance pattern. Early diagnosis is critical in MFS. Because of the large size of fibrillin-1 gene (FBN1), the uniqueness of mutations, and the absence of genotype-to-phenotype correlations linkage analysis can be very helpful for early diagnosis of MFS. In this study, eight polymorphic markers were evaluated among families related to an affected pedigree.
Materials and Methods
An extended family in Birjand, Iran, with numerous cases of Marfan Syndrome in three consecutive generations, is being reported. From all consented members of these families, peripheral blood samples were collected in tubes containing EDTA. DNA extraction was performed by the conventional salting-out method. Eight STR markers were selected for linkage analysis, including four intragenic markers (MTS1, MTS2, MTS3, and MTS4) and another four flanking FBN1 markers (D15S119, D15S126, D15S1028, and D15S143). PCR-amplified fragments were evaluated on 15% polyacrylamide gel.
Results
MTS1, MTS2, and MTS3 were informative in the extended pedigree. D5S1028 was the only non-MTS marker which showed an informative diagnostic capability.
Conclusion
MTS markers were informative and useful in the molecular diagnosis of Marfan Syndrome in an extended pedigree. MTS1, MTS2, and MTS3 can be used as a prenatal or presymptomatic diagnosis for all members of the extended pedigree.

Keywords


1. Dietz HC, Loeys B, Carta L, Ramirez F. Recent progress towards a molecular understanding of Marfan syndrome. Am J Med Genet C Semin Med Genet 2005; 139C:4-9.

2. Judge DP, Dietz HC. Marfan's syndrome. Lancet 2005 ; 366:1965-1976.

3. Gao LG, Luo F, Hui RT, Zhou XL. Recent molecular biological progress in Marfan syndrome and Marfan-associated disorders. Ageing Res Rev 2009; 9:363-368.

4. Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 1991; 352:337-339.

5. Sakai LY, Keene DR, Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol 1986; 103:2499-2509.

6. Judge DP, Dietz HC. Therapy of Marfan syndrome. Annu Rev Med 2008; 59:43-59.

7. Mizuguchi T, Matsumoto N. Recent progress in genetics of Marfan syndrome and Marfan-associated disorders. J Hum Genet 2007; 52:1-12.

8. Boileau C, Jondeau G, Mizuguchi T, Matsumoto N. Molecular genetics of Marfan syndrome. Curr Opin Cardiol 2005; 20:194-200.

9. Nollen GJ, Mulder BJ. What is new in the Marfan syndrome? Int J Cardiol. 2004 Dec; 97 Suppl 1:103-8.

10. Revencu N, Quenum G, Detaille T, Verellen G, De Paepe A, Verellen-Dumoulin C. Congenital diaphragmatic eventration and bilateral uretero-hydronephrosis in a patient with neonatal Marfan syndrome caused by a mutation in exon 25 of the FBN1 gene and review of the literature. Eur J Pediatr 2004; 163:33-37.

11. Davari M, Kazemi T, Alimirzaei H, Rezvani M. Cardiovascular Manifestation of a Family with Marfan’s Syndrome. J Teh Univ Heart Ctr? 2011; 6:37-40.

12. Judge DP, Biery NJ, Dietz HC. Characterization of microsatellite markers flanking FBN1: utility in the diagnostic evaluation for Marfan syndrome. Am J Med Genet 2001; 99:39-47.

13. Lee NC, Hwang B, Chen CH, Niu DM. Intrafamilial phenotype variation in Marfan syndrome ascertained by intragenic linkage analysis. J Formos Med Assoc 2005; 104:964-967.

14. Van Karnebeek CD, Naeff MS, Mulder BJ, Hennekam RC, Offringa M. Natural history of cardiovascular manifestations in Marfan syndrome. Arch Dis Child 2001; 84:129-137.

15. Gonzales EA. Marfan syndrome. J Am Acad Nurse Pract 2009; 21:663-670.

16. Hasan A, Poloniecki J, Child A. Ageing in Marfan syndrome. Int J Clin Pract 2007; 61:1308-1320.

17. Loeys B, De Backer J, Van Acker P, Wettinck K, Pals G, Nuytinck L, et al. Comprehensive molecular screening of the FBN1 gene favors locus homogeneity of classical Marfan syndrome. Hum Mutat 2004; 24:140-146.

18. Loeys B, Nuytinck L, Delvaux I, De Bie S, De Paepe A. Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome. Arch Intern Med 2001; 161:2447-2454.

19. Collod-Beroud G, Le Bourdelles S, Ades L, Ala-Kokko L, Booms P, Boxer M, et al. Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphism database. Hum Mutat 2003; 22:199-208.

20. Pereira L, Levran O, Ramirez F, Lynch JR, Sykes B, Pyeritz RE, et al. A molecular approach to the stratification of cardiovascular risk in families with Marfan's syndrome. N Engl J Med 1994; 331:148-153.

21. Mottes M, Mirandola S, Rigatelli F, Zolezzi F, Lisi V, Gordon D, et al. Allelic frequencies of FBN1 gene polymorphisms and genetic analysis of italian families with Marfan syndrome. Hum Hered 2000; 50:175-179.