Papers by Alper Gezdirici
Neurodevelopment and Genetic Evaluation of Sotos Syndrome Cases with a Novel Mutation: a Single-Center Experience
Journal of Molecular Neuroscience, Aug 12, 2021
Sotos syndrome is a non-progressive neurological disease with overgrowing, increased bone age, an... more Sotos syndrome is a non-progressive neurological disease with overgrowing, increased bone age, and developmental retardation. The aim of this study is to evaluate the prenatal, natal, and postnatal clinical findings of patients with Sotos syndrome. Sixteen patients suspected to have Sotos syndrome with clinical findings were examined retrospectively, ranging in ages between 3 and 23. In our file screening, we screened the FISH results of all 16 patients, but not all patients had NSD1 gene analysis results. We collected NSD1 gene analysis results, if there were any. The parameters that we investigated for these patients are birth weight, birth length, Apgar score at the 5th minute, dysmorphological face appearance, bone age, seizure, learning disability, feeding difficulties, surgical operation, and other accompanying abnormalities (brain MRI, abnormal echocardiographic findings, chronic otitis media, etc.). The anamnesis, clinical examination findings, and genetic reports of the patients were examined. For this, the hospital registration system was used. Breech presentation, Apgar score in the 5th minute of between 4 and 7, atrial septal defect at echocardiography, and consanguineous marriage rate were detected to be increased in individuals with Sotos syndrome compared to the normal population. When compared to the general population, delayed psychomotor development was determined. Macrocephaly, increased bone age, chronic otitis media frequency, and hernia operation frequency were determined to see if all patients were consistent with the literature. As a result of NSD1 gene sequencing analyses (NSD1 gene analysis was performed in 6 patients and a mutation was detected in 3 of them), three were found to have NSD1 gene mutation (one of them was novel). A novel deletion-type mutation that was not previously reported in the literature in the 19th exon of the NSD1 gene was determined. Xiphoidal protrusion was detected on this patient that had the novel mutation, and this situation has not been reported in the literature previously. If a patient has rapid growth, difficulty in learning, macrocephaly, speech delay, and timid personality, Sotos syndrome can be considered at the pre-diagnosis stage.
Medeniyet medical journal, Sep 21, 2022
Expanding the genotypic and phenotypic landscapes of rhizomelic chondrodysplasia punctata type 3 (RCDP3) with two novel families, and a review of the literature
American Journal of Medical Genetics, Aug 20, 2022
Acta Oncologica Turcica
Objective: In this study, it was aimed to determine the frequency of BRCA1 and BRCA2 variants in ... more Objective: In this study, it was aimed to determine the frequency of BRCA1 and BRCA2 variants in patients admitted to our clinic with hereditary breast-ovarian cancer and / or family history and to evaluate them in the light of the literature. Materials and Methods: All patients in our study were selected according to the current NCCN guideline test criteria. The Ion Torrent ™ Oncomine ™ BRCA Research Assay was used to sequence the coding regions of the BRCA1 and BRCA2 genes in our patients. In addition, all patients with copy number changes were confirmed with SALSA ® MLPA ® Probemix P002 BRCA1 and Probemix P090 BRCA2 (MRC Holland). Results: Variants (pathogenic, likely pathogenic, variants of uncertain clinical significance, and copy number variations) were detected in 39 of the 149 patients included in the study. Novel variants that were not previously described in the literature were detected in two patients, one of the BRCA1 and one of the BRCA2 gene, respectively. Conclusion: In our study, the incidence of BRCA1 and BRCA2 variants was found to be 26.1%. This rate was higher than previous studies conducted in Turkey. Further studies are needed to identify common variants in the Turkish population and to evaluate the pathogenity of variants of uncertain clinical significance.
Fetal left ventricular myocardial performance index measured at 11–14 weeks of gestation in fetuses with an increased nuchal translucency
Journal of Obstetrics and Gynaecology Research
ObjectiveThis study aimed to evaluate the effect of an increase in nuchal translucency (NT) thick... more ObjectiveThis study aimed to evaluate the effect of an increase in nuchal translucency (NT) thickness on the myocardial performance index (MPI) in fetuses without cardiac anomaly in the first trimester and to determine whether a difference in MPI between those with and without trisomy 21 in these fetuses could be determined.MethodsThe study group consisted of 53 pregnancies complicated with increased NT thickness without any associated structural anomalies. Forty‐six gestational age‐matched pregnant women whose fetuses had normal NT thickness were enrolled as the control group.ResultsIn the increased NT thickness group, the mean isovolumetric relaxation time (IRT) value (0.050 ± 0.011 s) was significantly higher and the mean ejection time (ET) value (0.149 ± 0.010 s) was significantly lower than those values in the normal NT thickness group (0.045 ± 0.005 and 0.155 ± 0.009 s, p = 0.023 and p = 0.009, respectively). We found a significantly higher mean left MPI value in the increased...
Journal of Academic Research in Medicine
Objective: Our goal was to evaluate the approach to the increased risk of fetal chromosomal anoma... more Objective: Our goal was to evaluate the approach to the increased risk of fetal chromosomal anomaly in pregnant women over thirty-five years of age. Methods: We retrospectively examined pregnant women over the age of 35 who underwent interventional procedures for fetal karyotype analysis in
Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome
Clinical Neurology and Neurosurgery
EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis
The American Journal of Human Genetics
Revista da Associação Médica Brasileira
OBJECTIVE: Chronic kidney disease (CKD) remains one of the major common health problems, and the ... more OBJECTIVE: Chronic kidney disease (CKD) remains one of the major common health problems, and the number of people affected by the disease is progressively increasing in Turkey and worldwide. This study aimed to investigate molecular defects in Alport syndrome (AS) and other genes in patients with clinically suspected CKD using whole-exome sequencing (WES). METHODS: Patients with clinical suspicion of CKD were included in the study. Molecular genetic analyses were performed on genomic DNA by using WES. RESULTS: A total of 15 with 5 different pathogenic or likely pathogenic variants were identified in CKD patients, with a diagnostic rate of 30%. Eight variants of uncertain significance were also detected. In this study, 10 variants were described for the first time. As a result, we detected variants associated with CKD in our study population and found AS as the most common CKD after other related kidney diseases. CONCLUSIONS: Our results suggest that in heterogeneous diseases such as CKD, WES analysis enables accurate identification of underlying molecular defects promptly. Although CKD accounts for 10-14% of all renal dysfunction, molecular genetic diagnosis is necessary for optimal longterm treatment, prognosis, and effective genetic counseling.
Genes
Hereditary disorders of connective tissue (HDCT) compromise a heterogeneous group of diseases cau... more Hereditary disorders of connective tissue (HDCT) compromise a heterogeneous group of diseases caused by pathogenic variants in genes encoding different components of the extracellular matrix and characterized by pleiotropic manifestations, mainly affecting the cutaneous, cardiovascular, and musculoskeletal systems. We report the case of a 9-year-old boy with a discernible connective tissue disorder characterized by cutis laxa (CL) and multiple herniations and caused by biallelic loss-of-function variants in EFEMP1. Hence, we identified EFEMP1 as a novel disease-causing gene in the CL spectrum, differentiating it from other HDCT.
Journal of Basic and Clinical Health Sciences
Purpose A number of mechanisms have been proposed for the effect of chromosomal translocations on... more Purpose A number of mechanisms have been proposed for the effect of chromosomal translocations on spermatogenesis and sperm maturation. However, there are still numerous ambiguous issues regarding these two processes. The aim of this study is to evaluate the effect of chromosome break areas on sperm count in the light of the literature. Material and Methods The study was conducted on the data of 16 male patients with reciprocal or Robertsonian translocation among 152 patients who were admitted to Adana Numune Training and Research Hospital and Kanuni Sultan Süleyman Training and Research Hospital Genetic Diagnosis Centers between 2013 and 2016 due to azoospermia and oligospermia. Results 11 of these patients had reciprocal and five patients had Robertsonian translocations. All the patients with Robertsonian translocations were detected with azoospermia. Of the patients with reciprocal translocation, five of them were azoospermic and six of them were severe oligospermic. Conclusion A...
Study of ten causal genes in Turkish patients with clinically suspected maturity-onset diabetes of the young (MODY) using a targeted next-generation sequencing panel
Molecular Biology Reports
Clinical and molecular genetic findings of Crisponi/cold‐induced sweating syndrome (CS/CISS) spectrum in patients from Turkey
Clinical Genetics
Medeniyet Medical Journal
Objective: This study aimed to demonstrate the diagnostic value of microarray testing in autism s... more Objective: This study aimed to demonstrate the diagnostic value of microarray testing in autism spectrum disorder, intellectual disability, and multiple congenital anomalies of unknown etiology, as well as to report some potential candidate genes for autism. Methods: Microarray analysis records between January 2016 and December 2017 from two Genetic Diagnostic Centers in Turkey, Kanuni Sultan Suleyman and Adana Numune Training and Research Hospital, were compiled. Detected copy number variations (CNVs) were classified as benign, likely benign, variants of uncertain significance (VUS), likely pathogenic, and pathogenic according to American College of Medical Genetics and Genomics guidelines. The clinical findings of the some patients and the literature data were compared. In 109 (24.5%) of 445 patients, a total of 163 CNVs with reporting criterion feature were detected. Sixty-nine (42%) and 8 (5%) of these were evaluated as pathogenic and likely pathogenic, respectively. Fifteen (9%) CNVs were also evaluated as VUS. Pathogenic or likely pathogenic CNVs were detected in 61 (13.6%) of 445 patients. We found that the probability of elucidating the etiology of microarray method in autism spectrum disorder, intellectual disability, and multiple congenital anomalies is 13.6% with a percentage similar to the literature. We suggest that the MYT1L, PXDN, TPO, and AUTS2 genes are all strong candidate genes for autism spectrum disorders. We detailed the clinical findings of the cases and reported that some CNV regions in the genome may be associated with autism.
Sağlık Bilimlerinde Değer
Amaç: Bu çalışmanın amacı, hastanemize tekrarlayan gebelik kaybı nedeniyle başvuran çiftlere uygu... more Amaç: Bu çalışmanın amacı, hastanemize tekrarlayan gebelik kaybı nedeniyle başvuran çiftlere uygun genetik danışmanlık verebilmek için hem majör kromozom anomalilerinin hem de trombofili parametrelerinin etiyolojideki rolünü araştırmaktır. Gereç ve Yöntemler: Çalışmamıza tekrarlayan gebelik kaybı nedeniyle Başakşehir Çam ve Sakura Şehir Hastanesi Genetik Hastalıklar Değerlendirme Merkezi'ne başvuran toplam 306 çift dâhil edildi. Tüm hastalarda kromozom analizleri ve 306 bayanda trombofili parametrelerinin analizleri gerçekleştirildi. Bulgular: Çalışmamızda toplam 306 çiftin 13’ünde (%4,25) polimorfizm dışında kalan kromozomal anomaliler tespit edildi. 4 hastada robertsonian translokasyon, 3 hastada resiprokal traslokasyon, 4 hastada mozaik kromozom kuruluşu, 1 hastada yapısal kromozal dengesizlik (derivatif kromozom) ve 1 hastada sayısal kromozal anomali varlığı tespit edilmiştir. Geriye kalan 293 çiftin kromozom analizi normaldi. Çalışmamızda trombofili parametreleri analiz edi...
Frontiers in Genetics
Laterality defects are defined by the perturbed left–right arrangement of organs in the body, occ... more Laterality defects are defined by the perturbed left–right arrangement of organs in the body, occurring in a syndromal or isolated fashion. In humans, primary ciliary dyskinesia (PCD) is a frequent underlying condition of defective left–right patterning, where ciliary motility defects also result in reduced airway clearance, frequent respiratory infections, and infertility. Non-motile cilia dysfunction and dysfunction of non-ciliary genes can also result in disturbances of the left–right body axis. Despite long-lasting genetic research, identification of gene mutations responsible for left–right patterning has remained surprisingly low. Here, we used whole-exome sequencing with Copy Number Variation (CNV) analysis to delineate the underlying molecular cause in 35 mainly consanguineous families with laterality defects. We identified causative gene variants in 14 families with a majority of mutations detected in genes previously associated with PCD, including two small homozygous CNVs...
Medeniyet Medical Journal, 2022
İkinci trimester Down sendromu tarama testlerindeki düşük östriyol (uE3) seviyesi, fetal ölüm, ko... more İkinci trimester Down sendromu tarama testlerindeki düşük östriyol (uE3) seviyesi, fetal ölüm, konjenital anormallikler veya fetüsün çeşitli genetik hormonal bozukluklarından kaynaklanabilir. Steroid sülfataz (STS) eksikliğine neden olan ve hafif iktiyozla seyreden bir mikrodelesyon sendromu olan X'e bağlı iktiyoz en yaygın genetik neden olmasına rağmen, ikinci trimester tarama testleri daha az yaygın ve daha şiddetli bir hastalık olan Smith Lemli Opitz Sendromu (SLOS) için risk hesaplamaktadır. Down sendromu taramasında uE3 düzeyi düşük olan gebeliklerin sonuçlarını araştırmayı ve bu gibi durumlarda SLOS yerine STS eksikliğinin yüksek prevalansını vurgulamayı amaçladık. Yöntemler: Tarama testlerinde uE3 seviyeleri çok düşük olan ve trizomi ve/veya SLOS açısından yüksek risk taşıyan on beş gebelik STS eksikliği ve SLOS açısından değerlendirilmiş ve test edilmiştir. Bulgular: Gebeliklerin yedisinde STS mikrodelesyon sendromu bulunurken, ek iki olguda aile ve/veya doğum sonrası öyküye dayanarak STS gen mutasyonu düşünüldü. Bir fetal ölüm tespit edildi. Ek kromozom anomalisi, SLOS veya konjenital malformasyon tespit edilmedi. Sonuçlar: SLOS çok ağır seyreden ve nadir görülen bir sendromdur. Tarama testlerinde SLOS için risk tahmini hamileler ve sağlık çalışanları için strese neden olmaktadır. Anksiyeteyi önlemek için tarama testlerinde düşük bir uE3 seviyesi tespit edildiğinde STS eksikliği için risk tahmininin eklenmesini öneririz.
Objective: We aimed to evaluate myocardial performance in fetuses with increased nuchal transluce... more Objective: We aimed to evaluate myocardial performance in fetuses with increased nuchal translucency. Method: Cases with increased NT without any associated structural anomalies were enrolled in this study. The study group consisted of 53 pregnancies complicated with thickened NT > 3.5 mm. Forty-six gestational age-matched pregnant women whose fetuses had normal NT thickness were enrolled in the study as the control group. The TEI index was evaluated before performing CVS in the group with an increase in NT. Karyotype analysis was performed via CVS in all patients with increased NT. In both groups, detailed fetal sonographic examinations, including fetal echocardiograms, were performed between 18 and 24 weeks of gestation. Results: The differences between normal and increased NT groups in terms of isovolumetric relaxation time (IRT), ejection time (ET), and myocardial performance index (MPI) variables were found to be statistically significant (p values of 0.023, 0.004, and < 0.001, respectively). For IRT and MPI variables, the median values of the group with an increase in NT were found to be significantly higher than that of the normal NT group, whereas the median value of the ET variable of the group with increased NT was significantly lower than that of the normal NT group Conclusion: The MPI significantly increased in the group with increased NT, but no difference was observed between those with and without Down syndrome. This suggests that increased NT is caused by cardiac dysfunction, whether or not Down syndrome is present.
Sağlık Bilimlerinde Değer, 2022
Amaç: Bu çalışmanın amacı, hastanemize infertilite nedeniyle başvuran erkeklere yardımcı üreme te... more Amaç: Bu çalışmanın amacı, hastanemize infertilite nedeniyle başvuran erkeklere yardımcı üreme tekniklerinden önce uygun genetik danışmanlık verebilmek için, azospermi ve/veya oligozoospermi etiyolojisine yönelik standart sitogenetik yöntemler ve Y kromozom mikrodelesyon analizleri ile hem majör kromozom anomalilerinin hem de Y kromozomu mikrodelesyonlarının sıklığı ve tiplerini araştırmaktır. Gereç ve Yöntemler: Çalışmamıza 2017-2020 yılları arasında erkek infertilitesi nedeniyle Kanuni Sultan Süleyman Eğitim ve Araştırma hastanemize başvuran toplam 437 hasta dâhil edildi. Tüm hastalar spermiogram, hormonal profil, kromozom analizi ve Y mikrodelesyon analizleri doğrultusunda değerlendirildi. Bulgular: Çalışmamızda toplam 437 hastanın 42’sinde (%9,6) kromozomal anomaliler tespit edildi. En sık görülen kromozomal anomali 47,XXY(Klinefelter sendromu) idi. 5 hastamızda dengeli translokayonlar vardı. 1 hastada ise marker kromozom tespit edildi. Geriye kalan 395 hastanın kromozom analizi...
Clinical, radiological and computational studies on two novel GNPTG variants causing mucolipidosis III gamma phenotypes with varying severity
Molecular Biology Reports, 2021
Mucolipidosis III gamma (ML III γ) is a slowly progressive disorder that affects multiple parts o... more Mucolipidosis III gamma (ML III γ) is a slowly progressive disorder that affects multiple parts of the body such as the skeleton, joints, and connective tissue structures. It is caused by pathogenic variants in the GNPTG gene that provides instructions for producing the γ subunit of GlcNAc-1-phosphotransferase. In this study we aim to characterize clinical findings and biological insights on two novel GNPTG variants causing ML III γ phenotypes with varying severity. We report on two siblings with ML III γ bearing the previously undescribed c.477C > G (p.Y159*) nonsense variant in a homozygous state as well as a patient with ML III γ bearing the novel c.110 + 19_111-17del variant in a homozygous state. These variants were revealed by whole-exome sequencing and Sanger sequencing, respectively. Their parents, who are heterozygotes for the same mutation, are healthy. The clinical and radiographic presentation of ML III γ in our patients who had c.477C > G (p.Y159*) variant is consistent with a relatively severe form of the disease, which is further supported by a working three-dimensional model of the GlcNAc-1-phosphotransferase γ subunit. On the other hand, it is seen that our patient who carries the c.110 + 19_111-17del variant has a milder phenotype. Our findings help broaden the spectrum of GNPTG variants causing ML III γ and offer structural and mechanistic insights into loss of GlcNAc-1-phosphotransferase γ subunit function.
Uploads
Papers by Alper Gezdirici