Moderate hearing loss and pseudodominant inheritance due to L90P/35delG mutations in the GJB2 (connexin 26) gene.

Mutations in the GJB2 (connexin 26-Cx26) gene are responsible for 20-50% of cases with prelingual non-syndromic deafness in a large part of the world including Turkey. Although most of the cases with Cx26 deafness have a recessive mode of inheritance, a small group of families demonstrated dominant or pseudodominant inheritance. In this report we present a Turkish family in which the proband had congenital profound deafness and was found to be homozygous for the 35delG mutation, whereas the father and a paternal uncle who had milder, late-onset sensorineural hearing loss had compound heterozygous 35delG and L90P mutations. This family and previous reports with the L90P mutation demonstrate that the hearing loss associated with the L90P/35delG genotype is consistently milder than that of 35delG homozygotes. GJB2 gene screening should be considered in families with seemingly dominant inheritance and late-onset moderate hearing loss.

Serum levels and differential expression of CD44 in childhood leukemia and malignant lymphoma: correlation with prognostic criteria and survival.

BACKGROUND: The CD44, a cell surface proteoglycan, participates in a variety of function including tumor dissemination and metastasis. However, there are no available data on the prognostic significance of CD44 expression of tumor tissue correlated with serum sCD44 level in childhood leukemias and lymphomas. METHODS: Serum levels and leukemic cell tumor tissue expression of CD44 were detected in 54 children with acute leukemia and malignant lymphoma. Serum samples were obtained from all patients before treatment and during remission. Twelve age-matched healthy children were included as a control group. RESULTS: The serum CD44 levels were significantly higher in patients with Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL) and acute lymphoblastic leukemia (ALL) than those in the control group. The median values were 1627.0, 1336.0, 1318.5, 1730.4, 902.7 ng/mL, respectively, and P<0.001, P<0.01, P<0.01, P<0.05 in comparisons, respectively. However, there was no significant difference between acute myeloid leukemia (AML) and the control group (median values: 900.3 and 902.7 ng/mL, respectively, P>0.05). Serum sCD44 levels significantly declined in HD, NHL and ALL patients who were in complete remission (median values: 684.0, 573.8 and 1101.1 ng/mL, respectively, P<0.05 in each comparison). Patients with HD had higher levels of serum sCD44 and correlated well with higher erythrocyte sedimentation rate (ESR), B-symptoms and advanced-stage disease (P<0.05, P<0.05 and P<0.01, respectively). Expression of CD44 was significantly high in patients with HD and NHL who were in advanced stages of disease. High serum CD44 level was also associated with high tumor tissue expression of CD44 in patients with HD and BL. In addition, patients with higher levels of serum sCD44, had a poorer outcome and survival than those with lower sCD44 levels in HD and NHL groups. CONCLUSIONS: A high serum sCD44 level and/or tumor tissue expression at diagnosis is associated with poor prognostic criteria and/or unfavorable outcome in childhood leukemias and lymphomas.

Connexin 26 (GJB2) mutations in the Turkish population: implications for the origin and high frequency of the 35delG mutation in Caucasians.

Mutations in the Connexin 26 (GJB2/Cx26) gene are responsible for more than half of all cases of prelingual non-syndromic recessive deafness in many Caucasian populations. To determine the importance of Cx26 mutations as a cause of deafness in Turks we screened 11 families with prelingual non-syndromic deafness, seven (64%) of which were found to carry the 35delG mutation. We subsequently screened 674 Turkish subjects with no known hearing loss and found twelve 35delG heterozygotes (1.78%; 95% confidence interval: 0.9%-3%) but no examples of the 167delT mutation. To search for possible founder effects, we typed chromosomes carrying the 35delG mutation for closely linked polymorphic markers in samples from Turkey and United States and compared the allele frequencies with those of hearing subjects. The data showed a modest degree of disequilibrium in both populations. Analyses of two pedigrees from Turkey demonstrated both conserved and different haplotypes, suggesting possible founder effects and multiple origins of the 35delG mutation.

Possible effects of antioxidant status on increased platelet aggregation in childhood iron-deficiency anemia.

BACKGROUND: Alterations in platelet function and antioxidant status in children with iron-deficiency anemia (IDA) have been reported previously. The present study was performed to better understand possible interactions between these two systems. METHODS: Erythrocyte superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activity and platelet function were evaluated in 15 children (aged 1 1/2-15 years) with IDA. The antioxidant enzyme activity was determined spectrophotometrically. Platelet aggregation and secretion studies were performed using impedance and bioluminescence methods, respectively. Ten age-matched healthy children were included as a control group. RESULTS: There were no differences in SOD and CAT activities between patients and controls. However, GSH-Px activity was significantly lower in the iron-deficient children. Platelet aggregation responses to collagen and ADP were also significantly higher in iron-deficient children than in controls. CONCLUSIONS: Decreased antioxidant defense in IDA may cause increased oxidant stress, which, in turn, may result in a tendency towards platelet aggregation.

Homozygous ß-Thalassemia (FCS8-AA) and Hereditary Spherocytosis in the Same Patient.

A three-year old Turkish girl having both homozygous ß-thalassemia and hereditary spherocytosis and her family have been studied. The molecular defect causing thalassemia in the family was of the frame shift codon 8 (-AA) mutation type. The diagnosis of hereditary spherocytosis is based on osmotic fragility test in the patient and the family. However, the examination of erythrocyte membrane proteins has not been possible. ßthalassemia is in the heterozygous form in the mother, the father, and in two sisters. The mother, the father, and one of the sisters also have hereditary spherocytosis in addition to thalassemia. All those family members are asymptomatic. However, the patient who has frame shift codon 8 homozygosity along with hereditary spherocytosis presented with a severe form of hemolytic anemia.

Hereditary multiple exostoses and acute myeloid leukemia: an unusual association.

Hereditary multiple exostoses (HME) is an autosomal dominant disorder characterized by the presence of multiple exostoses. Three genetic loci have been identified, of which two (EXT1 and EXT2) have tumor suppressor activity. HME greatly increases the risk to develop sarcoma in the dysplastic tissue. The authors report an 8-year-old girl with HME who developed acute myeloblastic leukemia.

Alternative diagnostic method for streptococcal pharyngitis: Breese scoring system.

This study was performed to determine the effectiveness of the Breese scoring system for the diagnosis of streptococcal pharyngitis with respect to different age groups. Two hundred and two children aged three years and younger (Group 1), and 514 children over three years old (Group 2) with complaints of acute pharyngitis were evaluated by Breese scoring and throat-swab cultures. In Group 1, no significant difference was detected in Breese scoring between subjects who had positive and negative culture for group A beta-hemolytic streptococci (GABHS). However, in Group 2 the mean value of the Breese scores was found to be higher in subjects who had positive GABHS. The diagnostic value of Breese scoring was examined for each group. Its sensitivity, and positive and negative predictive values were higher in Group 2 than in Group 1. In conclusion, Breese scoring was determined to be helpful in the diagnosis of streptococcal pharyngitis in children over three years of age.

Effect of plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish deep vein thrombotic patients with and without FV1691 G-A.

A decreased fibrinolytic activity due to increased levels of plasminogen activator inhibitor-1 has been shown in deep vein thrombosis patients. Elevated plasma plasminogen activator inhibitor-1 levels are associated with the 4G allele of a 4G/5G polymorphism located in the promoter region of the plasminogen activator inhibitor-1 gene. Because there is no existing data in the Turkish population, we aimed to study these mutations in patients with deep vein thrombosis (n = 136) and normal controls (n = 113), consecutively selected among unrelated healthy subjects without personal and familial history of atherothrombosis from Ankara, Turkey. DNA was extracted by conventional methods, and polymerase chain reaction of the plasminogen activator inhibitor-1 4G/5G polymorphism was performed according to a previously described method. Genotype distributions of FV 1691G-A and plasminogen activator inhibitor-1 4G/5G are as follows: plasminogen activator inhibitor-1 4G (patients) 0.562, plasminogen activator inhibitor-1 4G (controls) 0.50 (p = 0.6); FV1691A (patients) 0.147, FV1691A (controls) 0.035 (p = 0.005). Our data indicated that plasminogen activator inhibitor-1 4G/5G does not have an effect on the thrombotic risk. Carrying the 4G allele either in heterozygous or homozygous state increases the risk in the presence of FV1691A (odds ratio: 9.8 and 6.9, confidence interval 95% 2.9-32.7 and 1.3-35.8). FV1691A is an independent risk factor for thrombosis (odds ratio: 5.5, confidence interval: 95% 2.5-12.1). We concluded that coexistence of FV1691A and plasminogen activator inhibitor-1 4G allele leads to an increased risk for thrombosis leading a further evidence to another prothrombotic factor that may be necessary for the development of a manifest thrombotic event.

Effect of methylenetetrahydrofolate reductase 677 C-T, 1298 A-C, and 1317 T-C on factor V 1691 mutation in Turkish deep vein thrombosis patients.

Possible effect of three common mutations in (MTHFR 677 C-T; 1317 T-C; 1298 C-A) and FV 1691 G-A mutation was studied in Turkish patients with thrombosis and compared with normal controls. The case-control study included 68 patients with the diagnosis of deep vein thrombosis and 66 controls, consecutively selected among subjects without personal and familial history of atherothrombosis. Patients with deep vein thrombosis were selected if Doppler ultrasonography was positive. Only, the comparison of factor V 1691 G-A mutation revealed statistically significant difference in control (6.06%) and deep vein thrombosis (23.5%) group. Risk assessment of double prothrombotic gene alterations revealed only FV 1691 G-A mutation as an independent risk factor for thrombosis (odds ratio 4.7 [1.5-15.0]), but our data suggested that MTHFR 677 has effect on its own (odds ratio 1.97 [0.6-2.7]) but may have synergy with FV 1691 G-A (odds ratio 8.12 [2.0-25.3]). However, MTHFR 1298 A-C and 1317 T-C does not have any effect; furthermore, being heterozygote at two different loci or homozygosity at least in a locus for 677 and 1298 revealed a significant increase (odds ratio 9 and 24 [1.3-59.3 and 2.3-240.3]) between these two groups.

Multiple Cerebral Emboli in a Homozygous b-Thalassaemia Patient Due to Factor V 1299 (His-Arg) 4070 A-G Mutation.

Thromboembolic episodes are quite rare in beta thalassemia major patients although there is a tendency for thrombosis in haemolytic anaemias. We report a patient with cerebral thromboembolic episode triggered by a minor blood group incompatibility in which the underlying defect of factor V 1299 (His-Arg) was detected three years after his death.

Right atrial catheter-related complications in pediatric oncology patients: the situation in a developing country.

The complications of right atrial catheters (RACs) in pediatric oncology patients are unknown for centers in developing countries. This study examined the complications of RACs at Ankara University Medical School, Turkey. A total of 90 RACs were placed in 61 children for long-term chemotherapy with a total experience of 15,536 catheter days. The rate of catheter-related sepsis was 4.9 episodes per 1000 catheter days. Coagulase-negative staphylococci and Candida species were the most common organisms, accounting for 25.0 and 13.1% of all organisms, respectively. The most common reasons for the removal of the RACs were infection (42.4%) and dislodgement (32.2%). The rates of complications were significantly higher in this study than in western studies. This increase could be explained by the differences in catheter care practices in the Turkish center. In conclusion, the use of RACs in a developing country necessitates an appraisal of the benefits and risks for each patient and improvement of catheter care procedures.

Assessment of the efficacy and safety of paracetamol, ibuprofen and nimesulide in children with upper respiratory tract infections.

OBJECTIVE: The aim of this study was to assess and compare the efficacy and tolerability of paracetamol, ibuprofen and nimesulide in children with upper respiratory tract infections (URTIs). METHODS: Ninety children with acute URTIs and fever were enrolled to the study. The patients were allocated to three groups. The first group was treated with paracetamol 10 mg/kg thrice daily; the second group with ibuprofen 10 mg/kg thrice daily; and the third group received nimesulide 2.5 mg/kg twice daily for 5 days. RESULTS: The anti-pyretic activity of nimesulide was greater and more rapid than either paracetamol or ibuprofen. The number of patients with normal temperature was significantly greater in the first 2 days for the nimesulide group. The improvement in cough for the paracetamol group was better than the others. CONCLUSION: The results of this study demonstrated that the anti-pyretic effectiveness of nimesulide is better than paracetamol and ibuprofen in febrile children with URTIs. However, new studies in larger paediatric populations are required to explore the anti-inflammatory effect of nimesulide.

p53 Gene Polymorphisms in the Turkish Population.

There different RFLP's on the p53 gene were studied in a healthy Turkish population. These RFLP's were located on the exon 4 (CD 47), exon 6 (CD 213) and intron 6 (A-G). CD 47 (C-T) was not present. CD 213 (G) occurred very rarely with a frequency of 0.0114. The frequency of the Int 6 A/G a alteration was found to be 0.70 for "G". The heterozygosity rate was 32.72%.

Deletion polymorphism at the angiotensin-converting enzyme gene in Turkish patients with coronary artery disease.

Coronary artery disease (CAD) is a multifactorial disease in which genetic and environmental factors play an important role. These factors differ in each population. This study was carried out to determine whether there is an association between insertion/deletion (I/D) polymorphism and CAD in Turkish patients from Ankara. An I/D polymorphism in intron 16 of the gene coding for the angiotensin-converting enzyme (ACE) has been used to study the role of this gene in the aetiology of coronary atherosclerosis and hypertension. As there are no existing data for the Turkish population, we studied the I/D polymorphism of the ACE gene in 218 patients with CAD and 107 controls. Polymerase chain reaction (PCR) was used for genotyping the I and D alleles. The DD polymorphism of the ACE gene was significantly different between CAD subjects (0.733) and controls (0.612) (p=0.002). The observed heterozygosity was 29.3% and 43.9% and D allele frequency was 0.733 and 0.612, respectively. There was a significantly higher D allele (p=0.03) in 111 patients with myocardial infarction (MI) compared with controls. Furthermore, MI localization also gave a significance of p=0.002 for inferior MI but not for anterior MI (p=0.83). Forty-three hypertension patients had a D allele frequency of 0.767 which was significantly different from control (p=0.01). These data provide further evidence for the association of D allele and CAD in a Turkish population.

Search for genetic factors favoring thrombosis in Turkish population.

Common mutations in three genes (MTHFR 677 C-T; MS 2756 A-G; CBS Exon 8,844 ins 68) in homocysteine metabolism have been shown to cause increased plasma homocysteine levels thus causing a predisposition to thrombosis. FV 1691 G-A mutation, which is very common in the Turkish population, was also studied. As there is no existing data in the Turkish population, we aimed to study these mutations in patients with thrombosis and normal controls. The case-control study included 52 patients with the diagnosis of deep vein thrombosis (DVT) and 106 controls, consecutively selected among subjects without personal and family history of atherothrombosis. Patients with DVT were selected if Doppler ultrasonography was positive. The comparison of FV 1691 G-A mutation revealed statistically significant difference in control and DVT group. Risk assessment of double prothrombotic gene alterations indicated only FV 1691 G-A mutation as an independent risk factor for thrombosis, but our data suggested that MTHFR 677 has little effect on its own but may have synergy with FV 1691 G-A. Other possible risk genotypes at the homocysteine pathway did not have a significant effect on thrombosis. Furthermore, being heterozygote at two different loci or homozygosity at least in one locus also did not reveal a significant difference between these two groups in our population.

Homozygous protein C deficiency with a double variant His 202 to Tyr and Ala 346 to Thr.

We present the protein C gene analysis of a patient with homozygous protein C deficiency. The patient was referred with purpura fulminans 3 h after birth. Skin necroses had developed on the scalp, abdomen and upper extremities when he was two days old. His protein C activity was 0.03-0.05 IU/ml and the levels in his consanguineous parents were 0.32 and 0.40 IU/ml. He was treated initially with fresh frozen plasma, and later with daily oral anticoagulants, for two episodes of skin necrosis. He had three more episodes of skin necroses that were treated with intravenous protein C concentrate. He is now two years old and under treatment with daily coumarin 0.1-0.2 mg/kg per day to keep the International Normalized Ratio between 2.0-4.5. DNA analysis showed that he is homozygous for a double variant bearing His 202 to Tyr and Ala 346 to Thr mutations. His parents were each heterozygous for the double variant and were consanguineous. This mutation has been reported previously in an Austrian patient but this is the first homozygous case for this double variant.