Mohammed Rawashdeh

Genetic screening of fourteen mutations in Jordanian familial Mediterranean fever patients.

Familial Mediterranean fever is an autosomal recessive disorder characterised by episodic fever, abdominal and pleuritic pain, serositis and arthritis. The FMF gene (MEFV) has been mapped to chromosome 16p13.3 and generates a protein found exclusively in granulocytes. Seventeen mutations have been reported up to the present in FMF patients. This study involves the screening of 14 mutations in 42 Jordanian patients by two methods: RFLP and ARMS. The most frequent mutations were M694V and V726A (20% and 14% of the alleles respectively), followed by M680I and E148Q (9.5% and 7% of the alleles respectively). The A744S mutation accounts for 2.5% and the M694I, T267I and F479L mutations account each for 1% of the alleles. E167D, R761H, P369S, I692del and M694del mutations were not found in this population. Forty‐four percent of the alleles did not have any of the 14 mutations. The results show the diversity and the frequency of the mutations in the Jordanian patients, and open the way for further investigations on patients diagnosed to have FMF and in whom no mutations were found. Hum Mutat 15:384, 2000.

Familial Mediterranean Fever: association of elevated IgD plasma levels with specific MEFV mutations

Familial Mediterranean Fever (FMF) is a recessively inherited disorder, characterized by episodic fever, abdominal and arthritic pain, as well as other forms of inflammation. Some FMF patients present higher IgD serum levels, and it is not yet known whether such an elevation is related to specific genotypes or correlated with a specific phenotype. In order to evaluate the association between known FMF-related mutations and IgD levels in confirmed patients, as well as the correlation between those levels and the presence of specific clinical signs, genotypic analysis and IgD plasma measurements were performed for 148 Lebanese and Jordanian FMF patients. Most common mutational patterns were M694V heterozygotes (19%) and homozygotes (17%), and V726A heterozygotes (18%) and homozygotes (5%), with an additional 11% combining both mutations. Twenty-one patients had higher IgD levels (superior to 100 μg/ml). The risk for higher IgD levels was significantly associated with M694V homozygote status (OR = 6.25) but not with heterozygotic one (OR = 1). Similarly, the risk for higher IgD was also found with V726A homozygotes (OR = 2.2) but not with heterozygotes (OR = 1.05). The use of colchicine was not statistically associated with IgD levels. Clinically, hyper IgD was also found significantly associated with arthritis (OR = 18). Thus, homozygotic status for M694V, and to a lesser extent V726A, is associated with increased risk for higher IgD plasma levels, regardless of colchicine use. Elevated IgD plasma levels are also correlated with the severity of FMF manifestations, and especially with arthritis.

Bacteremia in Children: Etiologic Agents, Focal Sites, and Risk Factors

A prospective study was carried out on 210 cases of children under 10 years of age with fever. Cases of gastroenteritis, respiratory tract infections, and suspected sepsis in children seen or admitted to the pediatric hospital were studied. Clinical and microbiological data were recorded in a questionnaire or obtained from patient medical records. Most of the children with septicemia (71.3 per cent) were less than 1 year old. Focal source of bacteremia was gastroenteritis (40.4 per cent), pneumonia or bronchopneumonia (20 per cent), meningitis (7.4 per cent), and urinary tract infections (7.4 per cent). The predominant pathogens isolated from blood or stool specimens were gram-positive bacteria (53.3 per cent), mainly Streptococcus pneumoniae and coagulase-negative Staphylococcus spp. The gram-negative bacteria (45.6 per cent) were mainly Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Yersinia spp. One case of Candida albicans (1.1 per cent) was reported. Pasteurella pneumotropica was reported in two cases for the first time. The mortality rate was 4 per cent, mostly from septicemia cases. Long duration of hospitalization (> 10 days) and parenteral feeding were identified as risk factors. Resistance of the isolated pathogens to several commonly used antibiotics was observed. Empirical treatment with antibiotics is recommended only in life-threatening cases.

Shigellosis in Jordanian Children: a Clinico-epidemiologic Prospective Study and Susceptibility to Antibiotics

During a 2-year prospective study of children hospitalized with gastroenteritis, shigellosis was detected in 66 cases (9 per cent of 726 admissions). The age group for peak shigella incidence was 1-4 years. The incidence increased from 8 per cent in 1991, to 11 per cent in 1992. Shigella flexneri was the most common isolate (65 per cent), followed by Shigella sonnei (17 per cent), Shigella boydi (11 per cent), and Shigella dysenteriae (7 per cent). At presentation, 44 per cent had watery diarrhoea, followed by dysentery during hospitalization in the majority of cases. Seizures occurred in 27 per cent of cases and preceded diarrhoea in 15 per cent. Most Shigella flexneri and dysenteriae strains were resistant to co-trimoxazole, ampicillin, tetracyclin, and chloramphenicol. Nalidixic acid, gentamicin and cefotaxime were the most effective antibacterial agents. Case fatality was 3 per cent associated with strains resistant to the antibiotics used initially in the treatment.

Viral Gastroenteritis Among Young Children in Northern Jordan

During the summer months of 1992 and 1993, a total of 439 diarrhoeatic fecal specimens from infants and young children less than 3 years of age admitted to the pediatric ward of Princess Basma Teaching Hospital, northern Jordan were tested for the presence of viruses using direct electron microscopy (EM) and enzyme-linked immunosorbent assay (ELISA) for rotavirus. EM revealed rotaviruses in 83 (18.9 per cent) of cases, adenoviruses in five (1.1 per cent) cases, and small round viruses in three (0.68 per cent) cases. In contrast, the ELISA assay detected rotaviruses in 174 (39.6 per cent) of cases. In an evaluation of the collected diarrhoeatic fecal samples for rotavirus detected by ELISA, a sensitivity of 95.2 per cent and a specificity of 73.3 per cent was demonstrated.

Familial Mediterranean fever: the potential for misdiagnosis of E148V using the E148Q usual RFLP detection method

To the Editor: Familial Mediterranean fever (FMF) is a recessively inherited disease affecting mostly Mediterranean populations (1). Presently, 21 mutations (2–12) have been reported in the gene responsible for the disease, MEFV, mostly in exons 2 and 10. Previous studies on Lebanese and Jordanian FMF patients showed that these populations are genetically highly heterogeneous (13,14). In the present study, 342 Lebanese and Jordanian FMF patients were diagnosed according to Heller’s criteria (15). They willingly filled in an information form and donated blood. DNA was extracted from leucocytes by standard techniques (16). Sequencing of exons 2 (primers E2A: 5ƒAACTTTAATATCCAAGGGGATTC-3ƒ and E2B: 5ƒ-TTCTCTGCAGCCGATATAAAGTA3ƒ) and 10 (primers E10-1F: 5ƒ-AGAAGAACTACCCTGTCCCTG-3ƒ and E10-3R: 5ƒTAGTCACGGAATGCCGACTAG-3ƒ) using the ABI 310 genetic analyzer led to the identification of rare and novel mutations. Allelic frequencies of mutations M694V, V726A, M694I, M680I and E148Q were similar to those previously reported (13,14), whereas rare mutations, such as A744S (1 patient), R653H (2 patients), R761H (8 patients), M694del (1 patient) and E148V (1 patient), were encountered in the Lebanese series. New single nucleotide polymorphisms (SNP) corresponding to silent substitutions, such as G764 GGG/GGT in exon 10 and L142 CTG/CTT in exon 2, were

Genetic screening of fourteen mutations in Jordanian familial Mediterranean fever patients Communicated by: Mark H. Paalman Online Citation: Human Mutation, Mutation in Brief #310 (1999) Online http://journals.wiley.com/1059-7794/pdf/mutation/310.pdf

Familial Mediterranean fever is an autosomal recessive disorder characterised by episodic fever, abdominal and pleuritic pain, serositis and arthritis. The FMF gene (MEFV) has been mapped to chromosome 16p13.3 and generates a protein found exclusively in granulocytes. Seventeen mutations have been reported up to the present in FMF patients. This study involves the screening of 14 mutations in 42 Jordanian patients by two methods: RFLP and ARMS. The most frequent mutations were M694V and V726A (20% and 14% of the alleles respectively), followed by M680I and E148Q (9.5% and 7% of the alleles respectively). The A744S mutation accounts for 2.5% and the M694I, T267I and F479L mutations account each for 1% of the alleles. E167D, R761H, P369S, I692del and M694del mutations were not found in this population. Forty-four percent of the alleles did not have any of the 14 mutations. The results show the diversity and the frequency of the mutations in the Jordanian patients, and open the way for further investigations on patients diagnosed to have FMF and in whom no mutations were found. Hum Mutat 15:384, 2000.