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Gurbuz F.,Cukurova University | Damla Kotan L.,Cukurova University | Mengen E.,Cukurova University | Siklar Z.,Ankara University | And 17 more authors.
JCRPE Journal of Clinical Research in Pediatric Endocrinology | Year: 2012

Objective: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. Methods: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. Results: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. Conclusions: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty. © Journal of Clinical Research in Pedi atric Endocrinology, Published by Galenos Publishing.

Flanagan S.E.,University of Exeter | Xie W.,University of Exeter | Caswell R.,University of Exeter | Damhuis A.,Royal Devon and Exeter National Health Service Foundation Trust | And 20 more authors.
American Journal of Human Genetics | Year: 2013

Next-generation sequencing (NGS) enables analysis of the human genome on a scale previously unachievable by Sanger sequencing. Exome sequencing of the coding regions and conserved splice sites has been very successful in the identification of disease-causing mutations, and targeting of these regions has extended clinical diagnostic testing from analysis of fewer than ten genes per phenotype to more than 100. Noncoding mutations have been less extensively studied despite evidence from mRNA analysis for the existence of deep intronic mutations in >20 genes. We investigated individuals with hyperinsulinaemic hypoglycaemia and biochemical or genetic evidence to suggest noncoding mutations by using NGS to analyze the entire genomic regions of ABCC8 (117 kb) and HADH (94 kb) from overlapping ∼10 kb PCR amplicons. Two deep intronic mutations, c.1333-1013A>G in ABCC8 and c.636+471G>T HADH, were identified. Both are predicted to create a cryptic splice donor site and an out-of-frame pseudoexon. Sequence analysis of mRNA from affected individuals' fibroblasts or lymphoblastoid cells confirmed mutant transcripts with pseudoexon inclusion and premature termination codons. Testing of additional individuals showed that these are founder mutations in the Irish and Turkish populations, accounting for 14% of focal hyperinsulinism cases and 32% of subjects with HADH mutations in our cohort. The identification of deep intronic mutations has previously focused on the detection of aberrant mRNA transcripts in a subset of disorders for which RNA is readily obtained from the target tissue or ectopically expressed at sufficient levels. Our approach of using NGS to analyze the entire genomic DNA sequence is applicable to any disease. © 2013 The American Society of Human Genetics.

Guven A.,Goztepe Educational and Research Hospital | Ozgen T.,Ondokuz Mayis University | Gungor O.,Ondokuz Mayis University | Aydin M.,Ondokuz Mayis University | Baysal K.,Ondokuz Mayis University
JCRPE Journal of Clinical Research in Pediatric Endocrinology | Year: 2010

Objective: Sudden death has been reported in asymptomatic obese adults and the mechanism is unclear. In recent years, obesity has shown a dramatic increase in children and this enhances the risk factors for the development of cardiovascular disease. The aim of this study was to investigate whether there is repolarization abnormality and any potential risk factor such as increase in intima-media thickness (IMT) of carotid artery for corrected QT (QTc) prolongation among obese children. Methods: A total of 60 obese children, 30 of which had features of metabolic syndrome (MS), and 23 age-matched controls were included in the study. QTc interval was calculated at rest. The IMT of both common carotid arteries (CCA) was measured. The relationship between QTc, IMT of right and left CCA and insulin sensitivity indices were evaluated in the study group. Results: The QTc interval of the children with simple exogenous obesity (SEO) were longer than in the controls (p=0.024). The IMT of both carotid arteries of the obese girls and boys with and without MS were higher than the controls (p=<0.001). The QTc was significantly affected by the parameters pertaining to the right carotid artery IMT, to chronologic age and HDL-C. Conclusion: Since obesity may cause subclinical atherosclerotic disease regardless of sex, obese children must be followed closely for early cardiovascular problems. © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.

Acar C.,Acibadem University | Bilen C.,Hacettepe University | Bayazit Y.,Cukurova University | Aslan G.,Dokuz Eylul University | And 3 more authors.
Urology Journal | Year: 2014

Purpose: To compare the quality of life (QoL) of renal cancer patients following laparoscopic and open radical nephrectomy. Materials and Methods: Seventy-two (64.9%) patients who were treated with open radical nephrectomy (ORN group) and 39 (35.1%) patients who were treated with laparoscopic radical nephrectomy (LRN group) were included in this study. QoL was evaluated by Short Form-36 (SF-36) physical domain scores obtained before surgery, 1 and 6 months after surgery. Analgesic requirement and visual analog scale (VAS) pain scores following surgeries were recorded. Results: The demographic features of the groups were similar. There was a significant difference in tumor size between the ORN group (71.59 ± 29.83 mm) and LRN group (57.08 ± 19.33 mm) (P = .011). In the LRN group there was less blood loss, a lower transfusion rate, earlier ambulation, more rapid convalescence and shorter hospitalization; however, the difference in surgical duration between the ORN group (122.86 ± 36.8 min) and LRN group (140.17 ± 50.71 min) was not significant (P = .383). Analgesic requirement and VAS pain scores were similar in both groups. In terms of SF-36 physical domain scores, the general health perception score in the LRN group was higher than that in the ORN group at pre-surgery, 1 and 6 months after surgery. SF-36 physical functioning and general health perception scores in both groups were significantly lower in 1 month after surgery and were higher in 6 months after surgery, as compare to before surgery. Bodily pain scores in LRN group did not change significantly after surgery (P = .376). Conclusion: LRN exhibited some technical advantages, including less blood loss, shorter hospitalization and more rapid recovery. Although the ORN patients had relatively larger tumors, analgesic requirement, postoperative complications, body pain, and physical functioning weren't significantly different between the groups. QoL was higher 6 months after surgery than before surgery in both groups.

Verim A.,Haydarpasa Numune Educational and Research Hospital | Faruk Calim O.,Bezmialem Foundation University | Yenigun A.,Bezmialem Foundation University | Kocagoz G.D.,Bezmialem Foundation University | And 2 more authors.
Journal of Cranio-Maxillofacial Surgery | Year: 2012

Malformation of the inner nose is often found in conjunction with different types of cleft palate or may be seen with severe and complex craniofacial anomalies. Among such malformations, however, isolated vomer aplasia is rarely reported in the literature. This study sets forth our findings that congenital vomeral defect of the nasal septum is an isolated disorder with hereditary characteristics. Between 2001 and 2009, nine cases of isolated congenital vomeral bone defect were detected on endoscopic examination of patients referred to our clinic with nasal and otologic complaints. The files of these patients were reviewed and vomer aplasia was identified as an isolated hereditary condition with concomitant sinonasal symptoms. The defect of the posteroinferior part of the nasal septum was defined as a genetic disease presenting with no significant medical problems. Chromosomal analysis of these patients may help to reveal the relationship of this anomaly with different malformations of the maxillofacial complex. © 2011 European Association for Cranio-Maxillo- Facial Surgery.

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