The effect of HFE polymorphisms on cardiac iron overload in patients with beta-thalassemia major.

OBJECTIVE: We aimed to investigate the effect of human hemochromatosis protein (HFE) polymorphisms on cardiac iron overload in patients with beta-thalassemia major. METHODS: Our study included 33 patients diagnosed with beta-thalassemia major who were treated with regular transfusions and chelation therapy. M-mode, tissue Doppler, and pulsed wave Doppler echocardiography were performed on all patients. T2* magnetic resonance imaging (MRI) scans were also performed. The HFE polymorphisms (H63D, C282Y, S65C, Q283P, E168Q, E168X, W169X, P160delC, Q127H, H63H, V59M, and V53M) were studied using polymerase chain reaction. RESULTS: The H63D polymorphism was detected in six patients with beta-thalassemia major. Five patients were heterozygous for the H63D polymorphism, while one was homozygous. There were no other polymorphisms. There was no relationship between the HFE polymorphisms and either the serum ferritin levels or the T2-weighted MRI values (P > .05). Moreover, conventional echo and tissue Doppler echo findings were not correlated with the HFE polymorphisms. Pulmonary vein atrial reversal flow velocity, which is a manifestation of diastolic dysfunction measured with pulse wave echo, was higher in the patients with HFE polymorphisms (P = .036). CONCLUSIONS: The HFE polymorphisms had no effect on cardiac iron overload. However, pulmonary vein atrial reversal flow velocity measurements can provide important information for detecting diastolic dysfunction during cardiac follow-up of patients with HFE polymorphisms. Studies with more patients are needed to provide more information regarding this matter.

Homozygous mutation of CRLF-1 gene in a Turkish newborn with Crisponi syndrome.

Crisponi syndrome is a recently described rare autosomal recessive disorder. The main clinical features of the syndrome are neonatal onset of episodic contractions of the facial muscles with trismus and abundant salivation resembling a tetanic spasm. Herein, we report a case of 3-day-old male neonate presenting with trismus, abundant salivation, feeding difficulties, camptodactyly, and hyperthermia, which are consistent with the diagnostic criteria of Crisponi syndrome. The parents of the patient were consanguineous, supporting autosomal recessive inheritance. Molecular analysis revealed a homozygous mutation in cytokine receptor-like factor-1 gene in the patient.

Multidrug resistance 1 (MDR1) gene polymorphisms in childhood drug-resistant epilepsy.

Despite considerable progress in the pharmacotherapy of epilepsy, more than 30% of patients are reported to be resistant to antiepileptic drugs. Multidrug resistance 1 (MDR1) gene could play a role in drug resistance in epilepsy. In this study, the authors investigated the association between the MDR1 gene polymorphisms, C3435T and G2677AT, and drug resistance epilepsy by using polymerase chain reaction/restriction fragment length polymorphism and pyrosequencing methods in a group of 39 patients with drug-resistant epilepsy and 92 controls. No associations were found between the polymorphisms of the MDR1 gene and drug-resistant epilepsy. Haplotype analysis showed no significant association. Compound genotype analysis showed that CC3435/GG2677 was significantly higher in the control group compared to the patient group. In conclusion, MDR1 polymorphisms investigated in this study are not associated with antiepileptic drug resistance, but the CC3435/GG2677 compound genotype might have an effect on antiepileptic drug response.

The evaluation of the referral reasons of patients at a tertiary pediatric genetic center in Izmir, Turkey.

Our study aimed to review and evaluate the referral reasons of patients at Department of Pediatric Genetics, Ege University, between 1998 and 2006. In total, 2342 patients were referred to the pediatrics outpatient clinic for dysmorphological examination and suspected genetic conditions. The files were evaluated retrospectively, and they were grouped into five categories. The subgroups included mental retardation (MR)-multiple congenital anomalies and isolated anomalies in 1472 (62.85%), syndromes that may be associated with cytogenetic abnormalities in 634 (27.07%), suspected single-gene disorders in 134 (5.72%), suspected microdeletion syndromes in 48 (2.05%), and other genetic conditions comprising complex multifactorial disorders and ambiguous genitalia in 54 (2.31%). These data have provided useful information on the frequency of different groups of genetic diseases, genetic causes of MR, and the feasibility of genetic services. In conclusion, genetic service should be encouraged among physicians and patients in addition to the diagnosis, prognosis, and disease management efforts.

Prenatally diagnosed Turner syndrome and cystic hygroma: incidence and reasons for referrals.

OBJECTIVE: The objective of this study was to evaluate the incidence and reasons for referrals for prenatally detected Turner syndrome and cystic hygroma cases among prenatal cases performed between 1998 and 2007. METHODS: In this study 3,595 amniocentesis, chorionic villus and cordocenthesis materials obtained between 1998 and 2007 were evaluated. Among prenatal cases, 23 Turner syndrome cases were also evaluated according to their referral reasons. Among the indications of prenatal cases, cystic hygroma was evaluated according to karyotype results. RESULTS: Twenty-three cases were Turner Syndrome in which 7 cases were detected to have mosaic pattern. The indications for prenatal diagnosis for the cases were cystic hygroma in 11 cases, missed abortion in 6 cases, advanced maternal age in 5 cases and positive screening test results in 1 case. Among 18 cases having cystic hygroma detected by ultrasonography, 8 cases (44.4%) were found to have a 45,X karyotype, 3 cases were found to be mosaic Turner syndrome (16.7%), 5 cases (27.7%) had normal karyotype, 1 case (5.6%) 47,XX,+13 and 1 case (5.6%) 47,XX,+21. CONCLUSION: The present study indicates the importance of cystic hygroma in prenatal diagnosis of Turner Syndrome and other aneuploidies.

Febrile seizures: interleukin 1beta and interleukin-1 receptor antagonist polymorphisms.

In order to investigate the association between IL-1beta -511 C-->T and IL-1 receptor antagonist intron 2 variable tandem repeat polymorphisms, and febrile seizures in children, 90 children (mean age, 19.7 +/- 11.2 months) diagnosed with febrile seizure and 106 healthy controls (mean age, 14.2 +/- 3.6 months) with no seizure or neurologic events were included in the study. The polymorphisms were analyzed using restriction fragment length polymorphism and agarose gel electrophoresis methods. In the patient group, the frequencies of IL-1beta genotypes CC, CT, and TT were 24.4%, 52.2%, and 23.3%, respectively, compared with 38.7%, 50.95%, and 10.4%, respectively, in the control group. The TT genotype was significantly more common in the patient group than in the control group (P = 0.044), and the T allele frequency was significantly higher in the patient group (0.50 vs 0.36, P = 0.040). Among the three genotypes (RN1/1, RN1/2, and RN2/2) of the IL receptor antagonist gene variable tandem repeat polymorphisms, the frequency of both the RN2/2 genotype and the RN2 allele were significantly higher in the patient group (P = 0.007). Also RN2 allele frequency was found higher in patient group than controls (0.29 vs 0.15, P = 0.020). IL-1beta -511 and IL-1 receptor antagonist intron 2 variable tandem repeat polymorphisms may be involved in susceptibility to febrile convulsions in children.

Association of interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in Turkish children with atopic asthma.

Asthma is a complex genetic disease. Genetic and functional characteristics of interleukin (IL)-1 support a role as an asthma locus for the IL-1 family on chromosome 2q12-21. This study was performed to investigate the relationship between polymorphisms of IL-1beta promoter region -511C/T and IL-1 receptor antagonist (IL-1Ra) gene (IL-RN) and bronchial asthma in Turkish children. Children were divided into two groups: (1) bronchial asthma (n=328) and (2) healthy control (n=246). Polymerase chain reaction was used to resolve the IL-1beta -511C/T and the IL-1Ra intron 2 polymorphisms. Plasma IgE concentrations were measured by immunoassays, and skin-prick tests were done in children with atopic diseases. The number of genotype CC and C allele in the control groups in IL-1beta -511C/T polymorphisms increased. The number of genotype 1/1 in the asthma groups and genotypes 1/2 and 5/5 and 5 allele in the control groups in IL-1Ra intron 2 gene polymorphism increased. Serum spIgE level increased in the 2/2 genotype in the asthma groups in IL-1Ra intron 2 gene polymorphism. Based on these results, we conclude that there was an association of pediatric asthma with the IL-1beta -511C/T and IL-1Ra intron 2 gene polymorphism. Based on these findings, it has been proposed that IL-1beta -511C/T and IL-Ra intron 2 gene polymorphism are useful markers for prediction of asthma.

Congenital supratentorial cystic hemangioblastoma. Case report and review of the literature.

Supratentorial hemangioblastomas are rarely encountered tumors even in the pediatric population; an extensive review of the literature has revealed approximately 118 cases. However, only five of these occurred in infants, and three occurred during the first 2 months of life. A 5-week-old boy presented with emesis, irritability, a bulging anterior fontanelle, and a head circumference that had gradually expanded since birth. His medical and family histories were uninformative in terms of cancer or inherited diseases. Magnetic resonance imaging demonstrated a large loculated cyst with a heterogeneous contrast-enhancing 3-cm nodule, first pushing the left frontal and parietal lobes and then displacing into this region. After being exposed via a left frontoparietal craniotomy, the cyst was evacuated by a soft drain, and then the mass was totally excised. The histopathological diagnosis was a reticular variant of hemangioblastoma. Given that von Hippel-Lindau (VHL) gene mutations may be associated with hemangioblastomas, sequencing analysis of the VHL gene was performed; sequencing of the three exons of the VHL gene showed no exonic mutations. Clinical and neuroimaging follow-up of the patient have revealed an improved health status during the last 23 months. The authors reviewed the literature concerning congenital supratentorial hemangioblastomas, and they discuss the clinical and histopathological characteristics and differential diagnosis associated with such lesions.

Three circadian clock genes Per2, Arntl, and Npas2 contribute to winter depression.

BACKGROUND: Multiple lines of evidence suggest that the circadian clock contributes to the pathogenesis of winter depression or seasonal affective disorder (SAD). We hypothesized that sequence variations in three genes, including Per2, Arntl, and Npas2, which form a functional unit at the core of the circadian clock, predispose to winter depression. METHODS: In silico analysis of the biological effects of allelic differences suggested the target single-nucleotide polymorphisms (SNPs) to be analyzed in a sample of 189 patients and 189 matched controls. The most relevant SNP in each gene was identified for the interaction analysis and included in the multivariate assessment of the combined effects of all three SNPs on the disease risk. RESULTS: SAD was associated with variations in each of the three genes in gene-wise logistic regression analysis. In combination analysis of variations of Per2, Arntl, and Npas2, we found additive effects and identified a genetic risk profile for the disorder. Carriers of the risk genotype combination had the odds ratio of 4.43 of developing SAD as compared with the remaining genotypes, and of 10.67 as compared with the most protective genotype combination. CONCLUSION: Variations in the three circadian clock genes Per2, Arntl, and Npas2 are associated with the disease, supporting the hypothesis that the circadian clock mechanisms contribute to winter depression.

Ring chromosome 20 syndrome with intractable epilepsy.

Ring chromosome 20 (r[20]) syndrome is characterized by mild to moderate learning disability*, behavioural disorders, epilepsy, and various dysmorphic features. Although still considered rare, r (20) syndrome is being increasingly diagnosed. More than 30 cases have been described in the literature since 1976. Here we report an additional case of a 14-year-old male with r (20). He had moderate to severe learning disability and epileptic seizures manifesting at about 18 months of age. During the 13 years' follow-up period he showed intractable epileptic seizures, behavioural disorders, and mild dysmorphological features including microcephaly, strabismus, micrognathia, down-slanting eyelids, and ear abnormalities. Frequent episodes of atypical absence or non-convulsive status associated with electroencephalogram changes were seen in follow-up. He was treated with several classical and new antiepileptic drugs, including intravenous immunoglobulin, corticotropin, and vagal nerve stimulation, with unsuccessful control of seizures. Finally, surgical treatment (corpus callosotomy) was performed at the age of 13 years; severity of tonic seizures was diminished, but frequency was unchanged. Although his behavioural problems, e.g. hyperactivity, were mild in early childhood they became more severe when he was 11 years old. Aggressiveness, compulsiveness with self-injury, and panic attacks developed at the age of 13 years, and were more pronounced after callosotomy. This case report provides the first description of deterioration in psychological situation in patients with r(20) intractable epilepsy. The patient was diagnosed with r(20) syndrome after 13 years of clinical follow-up. Karyotype analysis should, therefore, be performed in every patient with intractable epilepsy of unknown aetiology.