Publications by authors named "Sebahat Yilmaz"

6 Publications

  • Page 1 of 1

Functional assessment of variants associated with Wolfram syndrome.

Hum Mol Genet 2019 11;28(22):3815-3824

Genetics and Genomic Medicine, UCL GOS Institute of Child Health, London, UK.

Wolfram syndrome (WS) is a heterogeneous multisystem neurodegenerative disorder with two allelic variations in addition to a separate subtype known as WS type 2. The wide phenotypic spectrum of WS includes diabetes mellitus and optic atrophy which is often accompanied by diabetes insipidus, deafness, urological and neurological complications in combination or in isolation. To date, the understanding of the genotype-phenotype relationship in this complex syndrome remains poorly understood. In this study, we identified and explored the functionality of rare and novel variants in the two causative WS genes WFS1 and CISD2 by assessing the effects of the mutations on the encoded proteins Wolframin and ERIS, in a cohort of 12 patients with autosomal recessive WS, dominant WS and WS type 2. The identified pathogenic variants included missense changes, frameshift deletions and insertions in WFS1 and an exonic deletion in CISD2 which all altered the respective encoded protein in a manner that did not correlate to the phenome previously described. These observations suggest the lack of genotype-phenotype correlation in this complex syndrome and the need to explore other molecular genetic mechanisms. Additionally, our findings highlight the importance of functionally assessing variants for their pathogenicity to tackle the problem of increasing variants of unknown significance in the public genetic databases.
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November 2019

Decreased retinal nerve fiber layer thickness in patients with congenital isolated growth hormone deficiency.

Eur J Ophthalmol 2014 Nov-Dec;24(6):873-8. Epub 2014 May 1.

Ulucanlar Eye Training and Research Hospital, Ankara - Turkey.

Purpose: To evaluate the optic disc topography parameters of children with congenital isolated growth hormone deficiency (GHD) using the Heidelberg retina tomograph (HRT) in a controlled study.

Methods: This prospective study included 32 eyes of 32 patients with congenital isolated GHD and 36 eyes of 36 healthy subjects. The topographic optic disc parameters (mean cup volume, rim volume, cup area, disc area, rim area, mean cup-to-disc ratio and cup depth, retinal nerve fiber layer thickness [RNFL]) were imaged in all subjects with HRT-III (software 3.01 a-M). Pearson correlation analysis was used to investigate the correlation between right and left eyes regarding the optic disc parameters. Differences between the 2 groups were evaluated by independent t test, Mann-Whitney U test, and chi-square test.

Results: The mean RNFL thickness in children with congenital isolated GHD was found to be statistically significantly thinner than in healthy subjects (p<0.05). However, no statistically significant differences were found between the mean cup volume, rim volume, cup area, disc area, rim area, mean cup-to-disc ratio and cup depth, and mean sectorial RNFL thickness (p>0.05).

Conclusions: The results suggest that congenital GHD may lead to thinner RNFL thickness when compared with healthy subjects. This indicates that GH has an important role in the development of the neural retina.
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December 2014

Corneal properties in children with congenital isolated growth hormone deficiency.

Int J Ophthalmol 2014 18;7(2):317-20. Epub 2014 Apr 18.

Department of Pediatric Endocrinology, Dr Sami Ulus Children's Health and Disease Training and Research Hospital, Ankara 06080, Turkey.

Aim: To compare the corneal parameters of children with congenital isolated growth hormone deficiency and healthy subjects.

Methods: In this cross-sectional, prospective study, 50 cases with growth hormone (GH) deficiency treated with recombinant GH and 71 healthy children underwent a complete ophthalmic examination. The corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated intraocular pressure (IOPcc) were measured with the Ocular Response Analyzer (ORA). Central corneal thickness (CCT) was measured by a ultrasonic pachymeter.

Results: The mean age was 13.0±3.0 years in the GH deficiency group consisting of 21 females and 29 males and 13.4±2.4 years in the healthy children group consisting of 41 females and 30 males. There was no statistically significant difference between the groups for gender or age (Chi-square test, P=0.09; independent t-test, P=0.28, respectively). The mean duration of recombinant GH therapy was 3.8±2.4y in the study group. The mean CH, CRF, IOPg and IOPcc values were 11.0±2.0, 10.9±1.9, 15.1±3.3, and 15.1±3.2 mm Hg respectively in the study group. The same values were 10.7±1.7, 10.5±1.7, 15.2±3.3, and 15.3±3.4 mm Hg respectively in the control group. The mean CCT values were 555.7±40.6, 545.1±32.5 µm in the study and control groups respectively. There was no statistically significant difference between the two groups for CH, CRF, IOPg, IOPcc measurements or CCT values (independent t-test, P=0.315, 0.286, 0.145, 0.747, 0.13 respectively).

Conclusion: Our study suggests that GH deficiency does not have an effect on the corneal parameters and CCT values. This observation could be because of the duration between the beginning of disease and the diagnosis and beginning of GH therapy.
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May 2014

Value of pelvic sonography in the diagnosis of various forms of precocious puberty in girls.

J Clin Ultrasound 2013 Feb 2;41(2):84-93. Epub 2012 Nov 2.

Dr. Sami Ulus Women and Children's Hospital, Department of Pediatric Radiology, Ankara, Turkey.

Purpose: To evaluate the role of pelvic sonography (US) in the diagnosis and differentiation of various forms of precocious puberty in girls, and to explore reliable cutoff points of pelvic US measurements for differentiating between these conditions.

Methods: Uterine length, uterine cross-sectional area, uterine volume, fundocervical ratio, and ovarian volumes of 143 healthy girls were compared with those of 125 girls with different forms of sexual precocity. Ovaries were morphologically classified as homogenous, paucicystic, multicystic, macrocystic, and isolated cystic.

Results: Almost all US measurements of girls with central precocious puberty in the 0- to 8-year age group were significantly increased compared with controls and girls with premature thelarche and adrenarche (p < 0.05, except for ovarian volumes in premature thelarche group), whereas no statistically significant difference was found in the 8- to 10-year group (p > 0.05). Ovarian morphology distributions did not differ significantly between patient subgroups, but all had more mature forms compared with controls. Due to the wide overlap between the measurements, no reliable cutoff points could be determined by charting receiver operating characteristics curves.

Conclusions: Pelvic US can improve the diagnosis of central precocious puberty in girls of 0-8 years of age but provides no reliable type differentiation alone. It provides no valuable information for this diagnosis in girls of 8-10 years of age.
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February 2013

High serum adiponectin levels during steroid-responsive nephrotic syndrome relapse.

Pediatr Nephrol 2005 Apr 3;20(4):474-7. Epub 2005 Feb 3.

Department of Pediatric Nephrology, Gazi University, Besevler, 06540 Ankara, Turkey.

Adiponectin (ADPN), exclusively expressed and secreted from adipocytes, is a recently discovered protein hormone with anti-atherogenic and anti-inflammatory properties in contrast to other well-known adipocytokines. It has independent negative associations with obesity and hyperinsulinemia/insulin resistance. Apart from chronic renal failure, nephrotic syndrome was suggested as the only renal disease condition associated with raised plasma ADPN levels in adults. We aimed to evaluate the effect of nephrotic state on serum adiponectin (ADPN) levels in pediatric patients with steroid-responsive nephrotic syndrome (SRNS) by comparing the levels in relapse and remission as well as in control subjects and documenting possible relationships between ADPN and proteinuria as well as serum protein/lipid parameters. 34 patients with SRNS and 22 healthy age, sex and BMI-matched control subjects were enrolled into the study. 15 of the 34 SRNS patients had active diseases, and these were known as the SRNS-relapse group (ten relapsed and five newly-diagnosed patients), while the remaining 19 were in complete remission (the SRNS-remission group). Serum ADPN levels, blood chemistry (protein/albumin, triglyceride (TG), cholesterol (Cho) and lipoprotein levels) and 24-hour proteinuria were studied. ADPN levels were determined by ELISA. As expectedly, there were significant alterations in serum protein-lipid parameters and 24-hour proteinuria levels in SRNS patients consistent with their disease activity. SRNS-relapse patients had substantially higher ADPN levels (36.77+/-15.06 (5.61-59.41, median 39.84) microg/ml), compared to those in SRNS-remission and control groups (14.17+/-6.02 (3.28-29.40, median 12.80) microg/ml and 11.84+/-7.53 (2.81-31.46, median 10.85) microg/ml, respectively, p=0.001). There were strong positive correlations between serum ADPN levels and Cho (r=0.637, p=0.000), TG (r=0.516, p=0.002), low density lipoprotein (r=0.614, p=0.000) levels and 24-hour proteinuria (r=0.828, p=0.000) levels, whereas protein (r=-0.695, p=0.000) and albumin (r=0.732, p=0.000) levels were inversely correlated with ADPN levels. Regression analysis showed a significant correlation between ADPN and proteinuria (p=0.000). In conclusion, remarkably increased serum ADPN levels were detected in SRNS-relapse compared to those in SRNS-remission. This phenomenon might be the reflection of a compensatory response to nephrotic state characterized by massive proteinuria, hypoalbuminemia and hyperlipidemia.
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April 2005