American Journal of Biomedical Research, 2016, Vol. 4, No. 1, 5-12
Available online at http://pubs.sciepub.com/ajbr/4/1/2
© Science and Education Publishing
DOI:10.12691/ajbr-4-1-2
Review of FBN1 Gene Role in Marfan Syndrome
Presentations Insilico Analysis
Mohanad Abdelrahim
1,2,*
, Khalid EL.Khalid
3
, Mohammed Elamin Faris
3
, Mohamed A.Hassan
2,4
,
Kamal Elsiddig
5
, Ahmed Siddig Muhammed
6
, Mohammed Nimir
7
, Mahil Abdalla
2
, Asgad Suliman
2
1
Departement of human anatomy faculty of Medicine University of Khartoum - Sudan
2
Daoud research group
3
MBBS university of Khartoum
4
Division of Molecular Genetics, university of Tubingen,- Germany
5
Deprtement of Surgery University of Khartoum - Sudan
6
Medical Student University of Khartoum - Sudan
7
Institute of endemic diseases - Khartoum - Sudan
*Corresponding author: mohanadkhalid91@gmail.com
Abstract Overview: This is translational bioinformatics was focused on analysis of single nucleotide
polymorphism of FBN1 gene and reviewing of the previous citations of the damaging SNPs. Introduction: Marfan
syndrome is a common autosomal dominant hereditary connective tissue disorder with variable presentations,
mutations in FBN1 gene were found to be responsible for Marfan syndrome and other related connective tissue
disorders, SNPs contributes to gene mutations and expression variations justifying phenotypic variations among
patients and hence such SNPs would be potential target for identification and analysis which may help in early
diagnosis of such life threatening disorder. Methods: computational methods were used on this work focusing on
analysis of SNPs in the coding regions of FBN1 gene found as non-synonymous variants (ns-SNP) and those in the
3’un-translated regions (3’UTR) affecting miRNA binding using computational methods including SIFT and
polyphen for analysis of (nsSNPs), prediction of not previously described SNPs was done using project hope
software, while (3’UTR) SNPs was analyzed using PolymiRTS tool functions interactions of FBN1 gene with
functionally similar gene were predicted using Genemania software. Results: Out of 1134 ns-SNPs analyzed 38
SNPs were found to damaging while analysis of 175 SNP in 3’UTR prove that 24 SNPs are disturbing to their target
sites and 46 SNPs are creating to new target sites.On reviewing of previous citation 31 of the predicted damaging
nSNPs were reported as mutations with specific Marfan syndrome presentation while 6 nsSNP were not previously
reported with high damaging probability.
Keywords: marfan syndrome, FBN1 gene, ns-SNPs, 3’UTR SNPs, sift, polyphene, PolymiRTS. project hope,
Genemania
Cite This Article: Mohanad Abdelrahim, Khalid EL.Khalid, Mohammed Elamin Faris, Mohamed A.Hassan,
Kamal Elsiddig, Ahmed Siddig Muhammed, Mohammed Nimir, Mahil Abdalla, and Asgad Suliman, “Review of
FBN1 Gene Role in Marfan Syndrome Presentations Insilico Analysis.” American Journal of Biomedical
Research, vol. 4, no. 1 (2016): 5-12. doi: 10.12691/ajbr-4-1-2.
1. Introduction
The Marfan syndrome is an autosomal dominant
disorder of the connective tissue shows striking pleiotropism
and clinical variability. The cardinal features occur in 3
systems--skeletal, ocular, and cardiovascular which is the
most serious signs and symptoms associated with
Marfansyndrome particularly aortic dilatation, dissection
and rupture and involvement of the aortic and mitral
valves, lead to a greatly reduced life expectancy [1,2].
1.1. FBN1 Gene
This gene encodes a member of the fibrillin family. The
encoded protein is a large, extracellular matrix glycoprotein
that serve as a structural component of 10-12 nm calcium-
binding micro fibrils. These micro fibrils provide force
bearing structural support in elastic and non-elastic
connective tissue throughout the body. Mutations in this
gene are associated with Marfan syndrome, isolated
ectopialentis, autosomal dominant Weill-Marchesani
syndrome, MASS syndrome, and Shprintzen-Goldberg
craniosynostosis syndrome. [Provided by RefSeq, Jul 2008].
Marfan syndrome is caused by mutations in the FBN1
gene on chromosome 15 [1], which encodes fibrillin-1, a
glycoprotein component of the extracellular matrix.
The fibrillin geneis located on chromosome 15, is
relatively large, and the coding sequence is divided into 65
exons. Described 3 alternatively spliced exons at the 5-
prime end, which they termed exon B, exon A, and exon C
[3,4]. A CpG island was identified that spans the first 2
alternatively spliced exons.Estimated the size of the FBN1
gene to be 200 kb [5].