الفهرس 
Genetic Thrombophilic Diseases.Only 14 pages are availabe for public view
 |  | from | 115 |  |  |
| | | from | 115 | | |
Abstract
CVT is a type of stroke where the thrombosis occurs in the venous side of the brain circulation.
Predisposition to CVT may have a genetic basis and inherited thrombophilias are known to cause 22.4% of
the CVT cases. The most recent meta-analyses published confirmed the association between FVL mutation
and the occurrence of CVT and also the association between prothrombin gene mutation and the occurrence
of CVT. However, these studies indicated that this association varied according to geographic regions. Data
from Arab world on the genetic risk factors for CVT is still developing. According to our knowledge no
previous research has previously documented this issue in Egypt. Our primary objective aimed to study the
role and prevalence of FVL mutation and prothrombin gene mutation as genetic risk factors for CVT in
Egyptian patients. Our second objective was to study the interaction of the presence of FVL mutation or
prothrombin gene mutation with the acquired risk factors for venous thrombosis in the occurrence of CVT
in Egypt.
This study was a case-control study that was carried out as a cooperation between the Neuropsychiatry
Department and the Medical Biochemistry and Molecular biology Department in our faculty of medicine
and university hospital. A total of 50 patients diagnosed with CVT were recruited in our study. Patients
were collected from the outpatient neuropsychiatric clinic or those who were admitted in the inpatient
neuropsychiatric wards directly from the Emergency Department (ED) of our Hospital in the period from
April 2020 to June 2021.The diagnosis was based on the clinical picture and confirmed by the radiological
investigations including computed tomography (CT), magnetic resonance imaging (MRI) and magnetic
resonance venography (MRV). Both sexes were included in the study with age <= 18 years old. We
excluded patients who had inconclusive radiological findings. Over the same period, one hundred and fifty
volunteers were recruited in the study as controls. They were matched with the patients in age, gender and
socioeconomic status, with no personal or family history of CVT or any other thromboembolism, and with
no biological relationship with the patients or with each other. So we had two groups: the CVT patients
group and the control group. Informed consent was obtained from the patients or their relatives if they
couldn’t do so and also informed consent was obtained from the controls before the collection of data.
Besides, the study was approved by the Local Ethics Committee in our faculty of medicine. The number/ID
of the approval is: 3/2020 NEUR 2. A designed questionnaire was filled by the subjects. It included details
regarding the demographic characteristics (as age, gender and marital status), symptoms and signs at time
of presentation (as headache, seizures, blurred vision, focal weakness or numbness, speech difficulty,
cranial nerve palsies and altered sensorium), and details of imaging modalities and radiological findings.
Female patients were inquired for pregnancy, puerperium, and usage of oral contraceptive pills OCPs or
hormone replacement therapy (HRT) as well.All subjects (patients and controls) were investigated for
routine laboratory investigations and thrombophilia screening information (including: lupus anticoagulants
(LAC), anticardiolipin antibodies (ACA), beta 2 glycoprotein I (β2GPI) antibodies, antinuclear antibodies
(ANA), antibodies to double stranded DNA (Anti ds-DNA)). Genetic screening included SNP detection for
FVL/G1691A mutation (rs6025) & prothrombin gene/G20210A mutation (rs1799963).
The results of our study demonstrated that: Out of 50 patients, six patients (12%) carried FVL mutation
(five were heterozygous and one was homozygous). Of the controls, six patients (4%) were heterozygous
for FVL mutation and no one was homozygous. The presence of FVL mutation was statistically significant
more in the cases than controls (P-value= 0.0489) & heterozygous plus homozygous carriers of FVL
mutation had a 3.273-fold increased risk of CVT (95% CI, 1-10.66), compared with participants who did
not carry the mutation. As regard the prothrombin gene mutation, ten patients (20%) carried the mutation
(six were heterozygous & four were homozygous), four controls (2.7%) were heterozygous carriers of the
prothrombin gene mutation, and no one of the controls was homozygous. The presence of prothrombin
gene mutation was highly statistically significant more in the cases than controls (P-value= 0.00019505) &
heterozygous plus homozygous carriers of prothrombin gene mutation had a 9.125 -fold increased risk of
CVT (95% CI, 2.7-30.6), compared with participants who did not carry the mutation.We studied the effect
of the combined presence of acquired risk factors (R.F) for CVT and the presence of either prothrombotic
variant (FVL or prothrombin gene mutation).Individuals who had no FVL or prothrombin gene mutation
and no acquired R.F for CVT were the reference category. Individuals carrying either prothrombotic
variants only (either FVL mutation or prothrombin gene mutation) and no acquired R.F had a 6.588-fold
increased risk of CVT (95% CI 2.748 -15.796 ) while those with both a prothrombotic variant and acquired
R.F had 28.778- fold increased risk of CVT (95% CI 6.258 - 132.332)