Subject ID | Country | Sex | Family History | Parental Consanguinity | HPO Terms | Variant | Zygosity | Mode of Inheritance | Reference | Remarks |
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306700.G.1 | Lebanon | Male | Yes | | Abnormality of coagulation | NM_000132.3:c.104A>G, NM_000132.3:c.277C>T, NM_000132.3:c.601G>A, NM_000132.3:c.679T>G, NM_000132.3:c.763G>A, NM_000132.3:c.1445T>G, NM_000132.3:c.1654T>C, NM_000132.3:c.6407G>A, NM_000132.3:c.5012G>A, NM_000132.3:c.5252A>G, NM_000132.3:c.6563G>A, NM_000132.3:c.3301G>T, NM_000132.3:c.6907C>T, NM_000132.3:c.1444-3C>G, NM_000132.3:c.602-3C>A, NM_000132.3:c.207_208del, NM_000132.3:c.2040_2043del, NM_000132.3:c.2830_2831del, NM_000132.3:c.4460del, NM_000132.3:c.6858_6868del | Hemizygous | X-linked, Recessive | Djambas Khayat et al. 2008 | 79 hemophilia patien... |
Other Reports
Algeria
In 1990, Nafa et al. investigated the allele frequencies of intragenic and extragenic F8 gene RFLPs in the Algerian population. For this, they analyzed 287 X chromosomes belonging to 97 males and 95 females. A new allele (14 kb), called 1 DZ, was found in 3.1% of the chromosomes. Only two obvious gene deletions were observed in 73 unrelated hemophiliacs. In a separate study, Nafa et al. (1992) found a novel mutation in a patient with 7% factor VIII activity and moderate hemophilia A.
Bahrain
Al-Arrayed et al. (Personal communication, Dubai, 2006) indicated that hemophilia is not a very common disease in Bahrain. Only 10 patients with hemophilia were under treatment at the Salmaniya Medical Complex at the time.
Egypt
Khalifa et al. (2000) described the expediency of using two intragenic micro-satellite repeat polymorphisms in introns 13 and 22 of F8 gene and (F8:C/vWF:Ag) ratio in identifying hemophilia A carriers. The study included 108 individuals from 19 Egyptian families. Of these, 23 females were considered to be obligatory carriers, 33 females were possible carriers, 25 females were normal, and 27 males had hemophilia A. All individuals were subjected to medical history, clinical examination, molecular studies, and coagulation studies [including bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (aPTT), F8:C, von Willebrand factor antigen estimation (vWF:Ag)]. In intron 13, six alleles were identified on both mutant and normal chromosomes which involved; (CA)20,21,24,25,26 and 27. The allele (CA)19 was detected in normal chromosomes only, whereas the alleles (CA)22 and 23 were identified only on mutant chromosomes, however, (CA)22 was the most frequent (24%). In intron 22, the (GT)(AG)25 and (GT)(AG)26 alleles were found in normal and mutant genes. (GT)(AG)25 was the commonest allele amongst normal chromosomes (50%), while (GT)(AG)26 allele was the most frequent amongst mutant ones (66%). The allele (GT)(AG)23 existed on a normal chromosome only and the allele (GT)(AG)22 was detected on a mutant chromosome only. By the use of both repeats in introns 13 and 22, diagnosis was possible for 13 families (68.4%), in which the obligatory carriers were heterozygous for the repeat (informative families). The use of (F8:C/vWF:Ag) ratio identified 91.3% of the obligatory carriers correctly. Of the possible carriers, only 24 could be identified by molecular analysis. Of these 24 possible carriers, 83.3% showed matched results with (F8:C/vWF:Ag) ratio. Khalifa et al. (2000) concluded that the molecular studies were powerful, if they were available and informative. However, in families with isolated cases or if the molecular studies had limitations, coagulation studies would be a better alternative.
[Khalifa AS, Shawky RM, El-Alfy MS, El-Danasoury AS, Rifaat MM, Ibrahim NA. Molecular Diagnosis of Hemophilia A Carriers in Egypt by Analysis of Two Intragenic Dinucleotide Repeat Polymorphisms. Egyptian J of Haematol. 2000; 25(1):51-66.]
[See Saudi Arabia > El-Bostany et al, 2008]
Iraq
In 1977, Al-Mondhiry studied the occurrence and pattern of inherited bleeding syndromes in Iraq. During the first fourteen months of a prospective on-going study at a major university center, 116 patients from 62 families were diagnosed as having inherited bleeding syndromes. All patients were referred because of moderate to severe bleeding diatheses. They included 62 hemophiliacs. In addition, 16 other hemophiliacs were also recognized among the pedigrees studied, but were not available for full investigations.
Al-Kubaisy et al. (2006) studied the seroprevalence of HCV infection among HIV-infected hemophiliacs in 47 HIV-infected hemophilia patients. Polymerase chain reaction and DNA enzyme immunoassay analyses indicated that seroprevalence of anti-HCV antibodies was 66.0%. Of 31 HCV/HIV co-infected patients, 21 (67.7%) had no history of blood transfusion. Al-Kubaisy et al. (2006) detected 4 HCV genotypes: 1a, 1b, 4 and 4 mixed with 3a, HCV-1b being the most frequent.
Jordan
[See: Saudi Arabia > Abu-Amero et al., 2008].
Kuwait
Sadek et al. (2000) reported a one-week old full-term infant male born with a birth weight of 3.5kg to a family with positive history of hemophilia. The patient was born to non-consanguineous parents with four healthy children (two males, two females) and a nine year old male with hemophilia. Following the second day of birth, the subject was screened for hemophilia; he was found to be asymptomatic and was discharged on the fourth day. The child did not demonstrate any odd bleeding following the collapse of the umbilical cord on the fifth day. Shortly, the patient grew to be irritable and hard to feed. After three days, the child reached the age of one week; he was taken to the hospital for assessment and was found to be hypoactive with full anterior fontanel cyanosis, which improved after the employment of suction and oxygenation. The subject was examined and demonstrated a head circumference (HC) of 37.6 cm, heart rate of 150/min, respiratory rate of 60/min, and BP of 87/55 mm HG. As a result he was moved to ICU for close examination; however he worsened and developed into sub consciousness with shallow breathing. The patient underwent arterial blood gas analysis which revealed respiratory acidosis that was dealt with using assisted ventilation. Furthermore, CT scan of the head confirmed the diagnosis of intracranial hemorrhage (ICH). Proper doses of cryoprecipitate were used to increase factor VIII level to an amount over 50 units/mL and a top-up of 45 mL of packed RBC were applied. Infusion of cryoprecipitate was carried on for a period of 16 days that followed the patient gaining consciousness, crying for feed, suckling well, moving all limbs with minor increase in the tone, and an overstated deep tendon reflexes. Recently at the age of three years, the patient underwent neurodevelopmental examination which revealed gross motor development delay with normal vision and hearing. Sadek et al. (2000) proposed estimation of plasma factor VIII levels, close clinical observation for any neurological characteristics, the employment of imaging for punctual diagnosis of ICH, and utilizing aggressive treatment for any suspected ICH.
Lebanon
Djambas Khayat et al. (2008) studied the spectrum of F8 mutations in 79 Lebanese patients with mostly severe Hemophilia A. Of these, 82% cases were familial.
Saudi Arabia
Abu-Amero et al. (2008) studied 20 unrelated Arab male patients from Syria (11), Jordan (1), Yemen (2), and Saudi Arabia (6) with severe hemophilia A, in order to study the spectrum of FVIII mutations among Arabs. The patients underwent detailed clinical examination and evaluation of their plasma FVIII:C activity. None of the patients showed a deletion of the FVIII gene. An attempt to detect intron 22 inversion by PCR revealed that 11 patients (55%) had the defect. The remaining nine patients were screened for FVIII gene mutations. Eight base substitutions (six of them novel) were detected in nine patients (45%), while none had any insertions or deletions. These mutations were 289S>L, 118T>P, 415G>D, 612N>I, 1603A>T, 1732K>R, 681S>Stop, and 655G>Stop. Polyphen database was used to determine the pathogenecity of each of these mutations. Apart from the 1603A>T mutation, all other changes were predicted to be pathogenic, which correlated well with the severe clinical phenotype observed. None of these mutations were detected in the control population. The mutations were spread all over the FVIII gene, and no particular hotspot could be identified. Mothers of five patients were tested for their carrier status. Two of these were found not to be carriers (289S>L, and 118T>P), suggesting a de novo mutation in the patients.
El-Bostany et al. (2008) recruited 43 children and adolescents from Saudi Arabia and Egypt with various bleeding disorders to assess the prevalence of inherited bleeding disorders (IBD). Their ages range from 1-18 years. They also included 15 matched controls. Extensive laboratory work-ups were made including complete blood count, coagulation studies and platelets functions. Of the patients, 26 had a positive family history of bleeding. Hemophilia A was diagnosed in 11 patients. Consanguinity was documented in seven of these 11 cases. About 30/43 cases experienced bleeding after dental procedures, and 15/43 had previous blood transfusion.
A study by Owaidah et al. (2009) evaluated genotype-phenotype correlation in hemophilia A patients in Saudi Arabia. Twenty two men affected with hemophilia A from 18 unrelated families were included in the study. All patients, with the exception of two (brothers), suffered from severe hemophilia A with FVIII activity less than 1 IU/dl. The age range was 4-37 years and all patients experienced frequent bleeding episodes. Screening for F8 intron 22 inversions showed that 10 out of 22 cases were positive for this mutation. The remaining 12 patients were then screened for other mutations in the gene F8. The latter analysis unveiled six different mutations (five missense and one deletion/insertion), of which one was a novel missense and one was a novel deletion/insertion. The two patients who suffered a mild phenotype were shown to have the missense c.923 C>T mutation, while all other patients suffered a severe phenotype.
Somalia
Abdulle et al. (1989) described five patients with severe hemophilia A. They were treated with fresh frozen plasma for bleedings. All of them were negative for antibodies to HIV. Abdulle et al. (1989) indicated that the potentialities of the Blood Transfusion Centre at Mogadishu at the time made it possible to produce amounts of cryoprecipitate sufficient to treat most of the patients living in the central region of the country where the capital, Mogadishu, is located.
Syria
[See: Saudi Arabia > Abu-Amero et al., 2008].
Yemen
[See: Saudi Arabia > Abu-Amero et al., 2008].