Semra Atalay

Mutations in OTOGL, encoding the inner ear protein otogelin-like, cause moderate sensorineural hearing loss

Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Here we present OTOGL mutations, a homozygous one base pair deletion (c.1430 delT) causing a frameshift (p.Val477Glufs(∗)25) in a large consanguineous family and two compound heterozygous mutations, c.547C>T (p.Arg183(∗)) and c.5238+5G>A, in a nonconsanguineous family with moderate nonsyndromic sensorineural hearing loss. OTOGL maps to the DFNB84 locus at 12q21.31 and encodes otogelin-like, which has structural similarities to the epithelial-secreted mucin protein family. We demonstrate that Otogl is expressed in the inner ear of vertebrates with a transcription level that is high in embryonic, lower in neonatal, and much lower in adult stages. Otogelin-like is localized to the acellular membranes of the cochlea and the vestibular system and to a variety of inner ear cells located underneath these membranes. Knocking down of otogl with morpholinos in zebrafish leads to sensorineural hearing loss and anatomical changes in the inner ear, supporting that otogelin-like is essential for normal inner ear function. We propose that OTOGL mutations affect the production and/or function of acellular structures of the inner ear, which ultimately leads to sensorineural hearing loss.

Dispersion of QT and QTc interval in healthy children, and effects of sinus arrhythmia on QT dispersion

Objective To determine the normal values of QT and QTc dispersion and the effects of sinus arrhythmia on QT dispersion in healthy children. Patients and setting The study was carried out in a university hospital on 372 local schoolchildren (200 male, 172 female), aged seven to 18 years. Methods The QT and preceding RR intervals of at least one sinus beat were measured manually in a range of nine to 12 leads on standard 12 lead surface ECGs. The corrected QT interval was computed by the method of Bazett. Dispersion of QT and QTc were defined as (1) the difference between the maximum and minimum QT and QTc intervals occurring in any of the 12 leads (QTD and QTcD), (2) the standard deviation of the QT and QTc interval in the measurable leads (QT-SD and QTc-SD). Results There was no significant difference in QT, QTc, and RR dispersion between girls and boys. Overall 53% of children had sinus arrhythmia. Although QTD and QT-SD were not affected by sinus arrhythmia, both QTcD and QTc-SD were significantly greater in children with sinus arrhythmia than in those without (QTcD: 52.9 (17.4) v40.9 (13.1); QTc-SD: 17.5 (5.9) v 13.2 (4.0); p < 0.001). Conclusions As calculation of QTc dispersion is affected by sinus arrhythmia, which is common in childhood, we suggest that QT dispersion should not be corrected for heart rate in children.

The value of the levels of acute phase reactants for the prediction of familial Mediterranean fever associated amyloidosis: a case control study

In order to determine the role of levels of acute phase proteins (APPs) for the development of amyloidosis in familial Mediterranean fever (FMF) patients, the levels of serum amyloid A (SAA), C reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate were measured in paired sera of 36 FMF patients during and in between acute attacks, 39 of their healthy parents (obligate heterozgotes), and 15 patients with FMF associated amyloidosis. To compare the levels of APPs, 39 patients with chronic infections or inflammatory diseases who may develop secondary amyloidosis, 20 patients with acute infections who are known to have elevated acute phase response but will never develop amyloidosis and 19 healthy controls were included. The median levels of all APPs are increased in the patients with FMF during attacks and a significant decrease was observed after the attack was over. The level of SAA was above reference range in all FMF patients during the attack free period and the level of at least one other APP was also above normal in 64% of the patients. Both CRP and SAA levels were found to be higher in obligate heterozygotes compared to controls. The levels of SAA in patients with FMF during the attack-free period, obligate heterozygotes and patients with FMF-amyloidosis were found to be similar. The levels in each group were found to be higher than SAA levels found in healthy controls yet lower than the levels measured in the patients with acute infections and patients with chronic inflammation or chronic infections. In conclusion, our results show that SAA level reflects subclinical inflammation with high sensitivity but its value for the prediction of amyloid formation process seems to be low.

Plasma endothelin-1 levels in patients with left-to-right shunt with or without pulmonary hypertension

The aim of this study was to evaluate the role of endothelin-1 (ET-1) in pathophysiology of pulmonary hypertension (PH) secondary to congenital heart disease with left-to-right shunt. Twenty-three children (12 male, 11 female) aged 0.58-13 years were enrolled the study. Blood samples were drawn from superior vena cava, right atrium, right ventricle, pulmonary artery and pulmonary wedge or pulmonary vein during cardiac catheterization. Plasma ET-1 levels were assayed by ELISA. Patients were divided into two groups according to the presence or absence of PH. Plasma ET-1 levels of the study group were compared to the peripheral venous and arterial ET-1 levels of 11 healthy infants and children (aged 0.75-13 years). Plasma ET-1 levels in patients with left-to-right shunt were found significantly higher than those of controls. However, plasma ET-1 levels were similar between the two groups of the patients. Pulmonary venous ET-1 levels were higher than the levels of superior vena cava, this suggested an increased production of ET-1 in pulmonary vascular bed in patients with PH. No correlations were found between plasma ET-1 levels and pulmonary arterial pressure, pulmonary vascular resistance and pulmonary blood flow in the patients. Plasma ET-1 levels of the patients with left-to-right shunt were increased independently from pulmonary arterial pressure and pulmonary vascular resistance. This increase was related to the production of ET-1 in pulmonary vascular bed in patients with PH. ET-1 could not be found to be directly related to the development of PH in the patients with left-to-right shunt.

Myocardial Tissue Velocities in Neonates

Background: Tissue Doppler echocardiography (TDE) has been applied to the children age group; however, myocardial tissue velocities of neonates have been reported by few researchers. Methods: Myocardial velocities along the longitudinal axis of the left ventricle were measured in two groups: 50 term neonates within 5 days after birth and 54 healthy children by TDE. Sample volumes were placed in mitral lateral annulus (MLA), mitral medial annulus (MMA), and in the basal and middle parts of the left ventricular lateral wall (LVLW) and interventricular septum (IVS). Results: The highest myocardial velocities were obtained from MLA. In all segments, the mean systolic velocity (Sw) was found significantly lower than the mean early diastolic (Ew) and atrial systolic velocities (Aw) (P < 0.0001). The mean Aw was the dominant component in the MMA and were significantly higher than Ew (P < 0.001). The mean Ew/Aw in the MMA and MLA increased significantly while replacing the Doppler beam from base to apex. TDE indexes of neonates, except Aw obtained from MLA and MMA, were significantly lower than that of children group (P < 0.0001 and P < 0.0001, respectively). The mean E/Ew ratio of the left ventricle in neonates was found to be significantly higher than that found in children group (P < 0.0001). Conclusion: In neonates, the diastolic and systolic myocardial velocities of the left ventricle were significantly lower than those measured in the children group. Decreased myocardial tissue values of neonates might be reflecting the immaturity of neonatal myocardium.

Autonomic nervous system functions in children with breath-holding spells and effects of iron deficiency.

Aim: To analyse the activity of the autonomic nervous system during breath‐holding spells, we assessed the ECG changes, including ventricular repolarization parameters before and during the spell. We also analysed the effects of iron deficiency on these ECG parameters. Methods: The study group consisted of 37 children with breath‐holding spells (30 cyanotic, 7 pallid) (mean age±SD: 12.9±10.8 mo). Twenty‐six healthy children (mean age±SD: 14.4±8.6 mo) served as a control group. All patients and controls had standard 12‐lead simultaneous surface ECG. All patients had ECG recordings during at least one severe breath‐holding spell obtained by “event recorder”. Traces obtained by “event recorder” were analysed in terms of mean heart rate and the frequency and duration of asystole during the spell. Results: Respiratory sinus arrhythmia on standard ECGs and asystole frequency during spells were higher in patients with pallid breath‐holding spells. Patients with iron deficiency had a lower frequency of respiratory sinus arrhythmia and prolonged asystole time during the spell. There was no difference in terms of ventricular repolarization parameters (QT/QTc intervals and QT/QTc dispersions) between patients and controls and between patient subgroups (cyanotic versus pallid).

Clinical and Epidemiological Characteristics of Children with Kawasaki Disease in Turkey

BACKGROUND Kawasaki disease (KD) is the leading cause of acquired heart disease in childhood in the developed countries. The objective of this study is to describe the clinical and epidemiological characteristics of children with KD in Turkey. METHODS The medical records of 24 patients treated for KD between January 1994 and June 2009 at Ankara University Medical School, Turkey were reviewed. RESULTS The male-to-female ratio was 1.4 : 1. The median age at diagnosis was 2 years (range: 6.5 months to 11 years). Conjunctivitis and changes in the lips and oral cavity were seen in 21/24 (87.5%), cervical lymphadenopathy 17/24 (70.8%), polymorphous rash 16/24 (66.7%) and peripheral changes in 12/24 (50%). Coronary artery abnormality (CAA) was observed in 8/24 (33.3%) cases. CAA was seen in both the complete and incomplete groups with similar frequency (31.3% vs. 37.5%, respectively). CONCLUSIONS KD must be kept in mind in the differential diagnosis of infants with prolonged fever.

The Effect of p.Arg25Cys Alteration in NKX2-5 on Conotruncal Heart Anomalies: Mutation or Polymorphism?

Heterozygous mutations in the NKX2-5 gene of patients with various congenital heart defects have been reported. Most of the congenital heart defects associated with the mutations in the NKX2-5 gene are conotruncal heart anomalies, primarily the tetralogy of Fallot. In this study, the authors screened 72 Turkish children with conotruncal heart anomalies and 185 healthy control subjects to find the NKX2-5 alterations. They found one previously documented NKX2-5 missense alteration, heterozygous c.73C>T (p.Arg25Cys), in a 10-year-old boy with tetralogy of Fallot. The same heterozygous alteration was found also in the patient’s healthy father and in two unrelated persons in the healthy control group. The current study shows for the first time the presence of p.Arg25Cys in healthy control subjects other than African Americans. These results show that no genetic support exists for the pathogenecity of this alteration, although a previous in vitro study and theoretical predictions suggest a structural/functional difference in the altered protein region.

Isolated recurrent pericarditis in a patient with familial Mediterranean fever.

Familial Mediterranean fever (FMF) should be kept in mind in the differential diagnosis of recurrent pericarditis and mutation analysis should be considered, especially in patients of Mediterranean origin.

Cardiac echinococcosis with multivisceral involvement

Cardiac hydatid cyst is an uncommon lesion. The infection, often acquired by children during play with infected dogs, is most common in sheep-raising areas of the world. We report our clinical and surgical experience in the treatment of one of the youngest reported cardiac hydatidosis patients with multivisceral involvement.