Molecular analysis of MEFV gene and factor v leiden mutations among Palestinian patients with Behçet’s disease

Dissertant

Abu Rumaylah, Hilal

Thesis advisor

Ayish, Suhayl

Comitee Members

Isawi, Tamir
Darwish, Hisham
Farraj, Muhammad A.

University

Birzeit University

Faculty

Faculty of Science

Department

Department Nutrition and Dietetics

University Country

Palestine (West Bank)

Degree

Master

Degree Date

2004

English Abstract

Behest's disease (BD) and familial Mediterranean fever (FMF), both inflammatory diseases, are highly prevalent in the Middle Eastern and Mediterranean populations.

BD is a multisystemic disorder with major manifestations of recurrent orogenital ulcerations, skin lesions, and uveitis, in which vasculitis plays an important pathogenic role.

BD is a polyfactorial disease closely associated with HLA-B51.

On the other hand, FMF is characterized by recurrent, short, self-limited episodes of fever, serosal inflammation manifested mainly by sterile peritonitis, pleurisy, and arthritis, and gradual development of nephropathic amyloidosis.

FMF is an autosomal recessive disease linked to a gene located on the short arm of chromosome 16, designated "MEFV".

It encodes a novel protein called "pyrin" or "marenostrin" that is expressed predominantly in neutrophils and monocytes and believed to play a role in inflammation and apoptosis. Considering the phenotypic and epidemiological similarities between FMF and BD, the inflammatory reactions that underlie the genesis of both diseases, and that factor V Leiden mutation may play a role in the hypercoagulable state in BD, we identified MEFV and factor V Leiden mutations in 44 Palestinian patients with Behçet's disease who did not meet the clinical criteria for FMF.

We screened for 34 MEFV mutations, 9 MEFV polymorphisms, and factor V Leiden mutation in 88 chromosomes from 28 definite BD patients (meeting the criteria of the International Study Group for BD), 12 probable BD patients (meeting at least two of these criteria), and 4 suspected BD patients (meeting at least one of these criteria). Four patients carried two mutated MEFV alleles, and fourteen had one mutated MEFV allele.

Altogether, 22 of the 88 chromosomes studied bore MEFV mutations/polymorphisms.

Furthermore, 18 BD patients (40.9%) had nine different MEFV mutations and two polymorphisms, which represent the sensitivity of testing these mutations in our samples.

V726A, M694V, M694I, and E148Q mutations and P706 polymorphism have been previously described in BD patients, whereas F479L, P369S, R408Q, and A744S mutations and F721 polymorphism are reported in BD patients for the first time in this study.

Interestingly, we identified a novel MEFV mutation that have not been reported before in either FMF or BD patients.

This mutation encodes a substitution of methionine for valine at position 722 (V722M).

In addition, factor V Leiden mutation was detected in only five of the forty four (11.4%) studied BD patients. This study is the first genetic analysis of the MEFV and factor V Leiden mutations among Palestinian BD patients.

It reflects the mutations profile in our BD patients.

Our results were in concordance with other studies in providing further data that MEFV gene mutations are an additional genetic susceptibility factor in BD, and therefore, the genetic testing for MEFV mutations may be advisable in the investigation of BD among patients of Mediterranean origin.

The population comprising this study may not be enough to role out the correlation between MEFV mutations and the clinical manifestations of BD on one hand, and factor V Leiden and venous thrombosis on the other hand.

Therefore, studies in large number of BD series are needed.

Main Subjects

Biology
Medicine

Topics

• Mouth
• Genital system
• Diseases

No. of Pages

119

Table of Contents

• APA
• MLA
• AMA

Language

English

Data Type

Arab Theses

Record ID

BIM-303718