Novel variants ensued genomic imprinting in familial central precocious puberty.

INTRODUCTION: Central precocious puberty (CPP) is characterized by the early onset of puberty and is associated with the critical processes involved in the pubertal switch. The puberty-related gene pool in the human genome is considerably large though few have been described in CPP. Within those genes, the genomic imprinting features of the MKRN3 and DLK1 genes add additional complexity to the understanding of the pathologic pathways. This study aimed to investigate the molecular etiology in the CPP cohort. METHODS: Eighteen familial CPP cases were investigated by Sanger sequencing for five CPP-related genes; DLK1, KISS1, KISS1R, MKRN3, and PROKR2. Segregation analysis was performed in all patients with pathogenic variants. Using an ELISA test, the functional pathogenicity of novel variants was also investigated in conjunction with serum delta-like 1 homolog (DLK1) concentrations. RESULTS: In three probands, a known variant in the MKRN3 gene (c.982C>T/p.(Arg328Cys)) and two novel variants in the DLK1 gene (c.357C>G/p.(Tyr119Ter) and c.67+78C>T) were identified. All three were inherited from the paternal allele. The individuals carrying the DLK1 variants had low detectable DLK1 levels in their serum. CONCLUSIONS: The frequencies were 5.5% (1/18) for MKRN3 11% (2/18) for DLK1, and none for either KISS1, KISS1R, and PROKR2. Low serum DLK1 levels in affected individuals supported the relationship between here described novel DLK1 gene variants with CPP. Nonsense nature of c.357C>G/p.(Tyr119Ter) and an alteration in the evolutionarily conserved nucleotide c.67+78C>T suggested the disruptive nature of the variant's compatibility with CPP.

SLC34A3 GENE MUTATION AS A RARE CAUSE OF HYPOPHOSPHATEMIA IN TWO SIBLINGS.

Context: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder, which is characterized by renal phosphate wasting, hypercalciuria, increased 1,25-dihydroxyvitamin D, and decreased parathormone (PTH) levels. Objective: Here we report different clinical features of two siblings with HHRH, confirmed with molecular diagnosis. Subjects and methods: 16.4 years old boy (P1), and 8.7 years old girl (P2) were referred to our outpatient clinic due to clinical suspicion of metabolic bone diseases. Results: P1 had severe hypophosphatemia. Additionally, PTH concentration was near to the lower limit, 1,25-dihydroxyvitamin-D concentration was near to the upper limit. P2 had relatively milder clinical and laboratory findings. Bilateral renal calculi were detected on ultrasound in both of them. HHRH was suspected due to their described biochemistry and the presence of bilateral renal calculi. Molecular analysis of SLC34A3 gene revealed a homozygous variant c.756G>A (p.Gln252=) and a splice donor variant c.1335+2T>A. After oral phosphate treatment, clinical and biochemical improvements were observed. However treatment nonadherence of patients was a barrier to reach treatment goal. Conclusion: The clinical phenotype due to the same mutation in the SLC34A3 gene may vary even among the members of the same family. An accurate diagnosis is important for the appropriate treatment.

Heart and Aorta Anomalies in Turner Syndrome and Relation with Karyotype.

OBJECTIVES: Turner Syndrome (TS) is associated with a high risk of cardiac anomalies and cardiovascular disease. We aimed to evaluate patients with TS (n=33) for cardiac and aortic pathology using thorax magnetic resonance angiography (MRA). SUBJECTS AND METHODS: Clinical findings, karyotypes, echocardiogram (ECHO) findings and thorax MRA results were evaluated. Aortic dimensions were measured and standard Z scores of aortic diameters along with aortic size index (ASI) were calculated. RESULTS: Mean age of the patients was 13.7±3.4 years. MRA revealed cardiovascular pathology in 10 patients (30%). CoA (n=4), aberrant right subclavian artery (n=3), dilatation of the ascending aorta (n=1), tortuosity of the descending aorta (n=1) and fusiform dilatation of the left subclavian artery (n=1) were found. Two of the four patients with CoA found on MRA were detected with ECHO. Mean diameter of the sinotubular junction was found to be elevated [mean±SD: 2.4±1.5]. Z scores for the diameters of the isthmus, ascending aorta and descending aorta were in normal ranges. 45,X patients were found to have significantly higher ASI values than non 45,X patients (p=0.036). CONCLUSION: Our findings indicate that patients with TS should be evaluated with MR imaging studies in addition to ECHO to reveal additional subtle cardiac and vascular anomalies. CoA which is very distally located or which has mild nature may not be seen by ECHO. The increase in ASI observed in 45,X patients may herald the development of life-threatening complications. Therefore, frequent follow-up is warranted in these patients.

THE ROLE OF THYROID FINE-NEEDLE ASPIRATION CYTOLOGY IN THE TREATMENT AND FOLLOW-UP OF THYROID NODULES IN THE PEDIATRIC POPULATION.

OBJECTIVE: Thyroid fine-needle aspiration (FNA) and cytology is a reliable diagnostic method used in the assessment of malignancy when evaluating thyroid nodules, in conjunction with clinical and ultrasonographic findings. The aim of this study is to compare clinical, ultrasonographic, cytological and histopathological findings in children who underwent thyroid FNA. METHODS: Subjects comprised 80 patients (52 female) aged 13.7±2.8 years at the time of FNA who where evaluated for thyroid nodules. Clinical, ultrasonographic and cytological findings of patients were evaluated retrospectively. RESULTS: Autoimmune thyroiditis was present in 30% and history of radiotherapy to the head or neck in 10%. The cytological diagnosis of patients included: inadequate or hemorrhagic sample in 10%; benign in 42.5%; atypia or follicular lesion of undetermined significance (AUS/FLUS) in 15%; suspicion of follicular neoplasia (SFN) in 7.5%; suspicion of malignancy (SM) in 8.8%; and malignant in 16.3%. Thirty-seven patients underwent thyroidectomy. Malignancy rates for histopathologic follow-up were 75%, 85.7% and 100% for SFN, SM and malignant categories, respectively. Only one benign and two AUS/FLUS FNAs were found to be malignant on histopathological examination. Among patients who had received radioiodinetherapy, 87.5% had malignancy. In this study, the sensitivity of FNA was 96%, specificity 50%, positive predictive value 90.9%, negative predictive value 75%, and diagnostic value of FNA was 89.2%. CONCLUSION: Thyroid FNA results were highly compatible with histopathological examination. Sensitivity, positive predictive value and diagnostic value of FNA were high.

Assessment of paediatric Hashimoto's thyroiditis using superb microvascular imaging.

AIM: To evaluate the role of superb microvascular imaging along with greyscale and Doppler imaging for thyroid gland evaluation in Hashimoto's thyroiditis (HT) versus control subjects. MATERIALS AND METHODS: The study included 33 healthy volunteers with normal ultrasound and laboratory findings and 70 patients with HT based on laboratory and sonographic findings who were undergoing follow-up and receiving medical treatment. HT patients were classified based on the modification of the scheme proposed by Sostre and Reyes that incorporates the extent of hypoechoic foci or patchy infiltration as grade A (foci involving <50% of the gland) and B (foci involving >50% of the gland). Thyroid volume, mean resistive indices, peak-systolic and end-diastolic velocities based on Doppler imaging, and vascularity index via superb microvascular imaging were obtained using a Canon Aplio 500 ultrasound device using a linear 10-14 MHz transducer. RESULTS: Patients with HT had significantly higher median thyroid volume and peak-systolic velocities (7.32 ml and 19 cm/s, respectively) compared to control subjects (4.62 ml and 16 cm/s, respectively). HT patients had significantly higher median vascularity index (VI; 13.5%) compared to control subjects (7.95%). A significant fair positive correlation with VI and anti-thyroglobulin antibody levels (r=0.356, p<0.05) and significant moderate positive correlation with VI and anti-thyroid peroxidase antibody levels (r=0.503, p<0.05) were found. In HT diagnosis, the optimal VI cut-off value was 10.58% with a sensitivity and specificity of 67.1% and 90%, respectively. CONCLUSION: Superb microvascular imaging appears to allow assessment of subtle vascularity changes in early HT stages that cannot be detected by Doppler parameters. This technique demonstrates excellent visualization of the microvascular structures and quantitative assessment based on a novel parameter such as VI.

The relationship between sleep duration and obesity in Turkish children and adolescents.

AIM: To determine the relationship between sleep duration and obesity in Turkish children and adolescents. METHODS: This study was conducted in Turkey with 5358 children aged 6 to 17 years. Height, weight, waist circumference (WC), mid-upper arm circumference (MUAC), triceps skinfold thickness were measured. Body mass index (BMI), arm fat area were calculated. Self-reported sleep duration by parents were obtained. RESULTS: As sleep duration increased, BMI, which was significantly higher in girls sleeping < or =8 h, decreased (p < 0.05). WC, MUAC, BMI were significantly higher in boys sleeping < or =8 h versus males sleeping > or =10 h. Boys sleeping < or =10 h in 6.0-17.0-years had significantly higher risk of overweight/obesity. In 6.0 to 17.0 years, the risk of overweight/obesity in boys sleeping 9-10 h, 8-9 h and < or =8 h were 1.86-, 1.74- and 2.06-times higher respectively, versus children sleeping > or =10 h (p < 0.05). CONCLUSION: Sleep duration may be an important factor for obesity and providing > or =10 h of sleep is recommended as a prevention strategy for obesity.

Attitudes and behaviours of students from the faculty of theology regarding organ donation: a study from Turkey.

The aim of this study was to investigate the knowledge and attitude of students from the Faculty of Theology of Erciyes University regarding organ donation. This study comprising all students (n = 264) showed that 51.6% of subjects to the kidney is an organ that may be donated; other organs were less known. 16.5% of the students thought that organ donation is not in accord with Islamic beliefs; 22.0% thought that it is permitted in Islam for Muslims to donate to non-Muslims, and 23.6% were willing to accept organs from non-Muslims. 23.6% of the students were willing to donate their organs, whereas 57.3% were undecided. None of the students had an organ donation card. Among students who did not consider donation or were undecided, 16.5% stated that it was "religiously inappropriate" and 13.3% stated that they did not "approve the loss of body integrity." Students declared that they had little knowledge regarding organ/tissue donation: 67.9% about the religious aspect, 78.9% about the legal aspect, and 80.5% about the scientific aspect. Only 24.6% of the group noted school education as their source of information, with 51.2% stating that they had been questioned about organ donation by society. With this study, we concluded that the student's knowledge regarding organ donation was not sufficient.

Haemophilus influenzae type b carriage among 3- to 24-month-old Turkish children.

There are few studies from developing countries on the epidemiology of Haemophilus influenzae (Hib) infections among infants and children. We set out to determine the prevalence of oropharyngeal Hib colonization among Turkish children younger than two years of age and to identify antimicrobial resistance among the isolates. A cross-sectional study was conducted on 818 healthy children and oropharyngeal secretions were sampled. The carriage rate of Hib was found to be 7.2% and this increased significantly with age. Carriage of Hib among 3- to 6-month-old children (3.5%) was higher than expected and was significantly higher among children who were passive smokers (P=0.04). Logistic regression analysis showed that breastfeeding status was the sole significant factor for colonization (OR 2.2, 95% CI 1.26-3.82). Antimicrobial susceptibility tests on 56 isolates of H. influenzae showed that 51.8% and 21.4% were resistant to trimethoprim-sulphamethoxazole and ampicillin respectively. Other notable resistances were to cefalexin (10.7%) and chloramphenicol (3.6%); no isolates were resistant to ceftriaxone.