Yazar "Dogan, Mustafa" seçeneğine göre listele
Listeleniyor 1 - 13 / 13
Sayfa Başına Sonuç
Sıralama seçenekleri
Öğe Bialelic Pathogenic (c.830G>A(p.R277Q)) Variant Disrupting the GNE Gene Function and Causes Nonaka myopathy Phenotype(Pleiades Publishing Ltd, 2023) Dogan, Mustafa; Akbulut, Ekrem; Gezdirici, Alper; Eroz, Recep; Bozdogan, Sevcan TugNonaka myopathy (MIM 605820) is caused by homozygous pathogenic variants in the GNE gene. It is a recessively inherited early adult-onset myopathy that usually preserves the quadriceps and presents with bilateral foot drop, usually caused by anterior tibialis weakness. In patients with Nonaka myopathy, serum creatine kinases are slightly elevated, muscle weakness progresses slowly, and ambulation loss develops after 15-20 yr. The current study aims to raise awareness of Nonaka myopathy that occurs as a rare phenotype due to pathogenic variants in GNE gene. Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and co-segregation analysis of the family were done by Sanger sequencing. Also the homology model of the mutant protein was created with the ProMod3 algorithm. We identified a bialelic pathogenic variant (c.830G>A) in GNE gene, which explain the patients' clinical status. We present the main findings of two siblings with Nonaka myopathy together with detailed clinical and genetic profiles of the patients together with a three-dimensional mutant GNE protein model. We think that the clinical characteristics and the effect of the (c.830G>A) variant will facilitate our understanding of GNE gene in Nonaka myopathy pathogenesis.Öğe Biallelic novel CCDC186 loss-of-function variant disrupting the gene function causes neurodevelopmental phenotype and review of the literature(Elsevier, 2025) Gezdirici, Alper; Turk, Sultan Buse; Esen, Tuna Eren; Yavas, Cuneyd; Akbulut, Ekrem; Yilmaz, Halil Ibrahim; Dogan, MustafaBackground: Coiled-coil domain-containing protein 186 (CCDC186) is essential for the transport of secretory dense-core vesicles (DCVs), specialized organelles responsible for storing and releasing neurotransmitters and other modulatory molecules in neurons and endocrine cells, thereby playing a crucial role in physiological processes such as synaptic plasticity, neurotransmission, and hormonal regulation. Resent reports have suggested that biallelic loss-of-function (LOF) variants in CCDC186 may be associated with neurodevelopmental disorders and a range of systemic manifestations. Methods: Whole exome sequencing (WES) was performed, and co-segregation analysis of the family was conducted using sanger sequencing. Additionally, five patients with CCDC186-associated phenotypes previously described in the literature were evaluated. Followed by cDNA synthesis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to analyze gene expression levels. Bioinformatics tools, including RoseTTAFold for protein modeling and STRING for protein-protein interaction networks, were employed to assess the structural and functional consequences of the mutation. Results: We identified a homozygous NM_018017.4:c.535C>T (p.Arg179Ter) nonsense variant in the CCDC186 gene. This variant was associated with a marked downregulation of CCDC186 expression in the proband, with moderate reductions observed in heterozygous family members, suggesting dysregulated gene expression resulting from the mutation. Protein modeling indicated structural alterations, including a shift from intrinsically disordered regions to helix-loop-helix motifs in the mutant protein, as well as reduced binding probabilities for most interacting partners. Conclusion: In this study, we presented the comprehensive clinical and genetic profiles of a Turkish child with a novel CCDC186 variant, along with five previously reported patients from the literature. Our findings support that the homozygous LOF variants of the CCDC186 gene are associated with a novel neurodevelopmental phenotype.Öğe Biallelic Novel USP53 Splicing Variant Disrupting the Gene Function that Causes Cholestasis Phenotype and Review of the Literature(Karger, 2023) Gezdirici, Alper; Sengul, Ozlem Kalaycik; Dogan, Mustafa; Ozguven, Banu Y.; Akbulut, EkremIntroduction: Hereditary cholestasis is a heterogeneous group of liver diseases that mostly show autosomal recessive inheritance. The phenotype of cholestasis is highly variable. Molecular genetic testing offers an useful approach to differentiate different types of cholestasis because some symptoms and findings overlap. Biallelic variants in USP53 have recently been reported in cholestasis phenotype. Methods: In this study, we aimed to characterize clinical findings and biological insights on a novel USP53 splice variant causing cholestasis phenotype and provided a review of the literature. We performed whole-exome sequencing and then confirmed it with Sanger sequencing. In addition, as a result of in silico analyses and cDNA analysis, we showed that the USP53 protein in our patient was shortened. Results: We report a novel splice variant (NM_019050.2:c.238-1G>C) in the USP53 gene via whole-exome sequencing in a patient with cholestasis phenotype. This variant was confirmed by Sanger sequencing and was a result of family segregation analysis; it was found to be in a heterozygous state in the parents and the other healthy elder brother of our patient. According to in silico analyses, the change in the splice region resulted in an increase in the length of exon 2, whereas the stop codon after the additional 3 amino acids (VTF) caused the protein to terminate prematurely. Thus, the mature USP53 protein, consisting of 1,073 amino acids, has been reduced to a small protein of 82 amino acids. Conclusion: We propose a model for the tertiary structure of USP53 for the first time, and together with all these data, we support the association of biallelic variants of the USP53 gene with cholestasis phenotype. We also present a comparison of previously reported patients with USP53-associated cholestasis phenotype to contribute to the literature.Öğe Clinical Characteristics and Genetic Analyses of Patients with Idiopathic Hypogonadotropic Hypogonadism(Galenos Publ House, 2023) Ciftci, Nurdan; Akinci, Aysehan; Akbulut, Ekrem; Camtosun, Emine; Dundar, Ismail; Dogan, Mustafa; Kayas, LemanObjective: Idiopathic hypogonadotropic hypogonadism (IHH) is classified into two groups-Kalman syndrome and normosmic IHH (nIHH). Half of all cases can be explained by mutations in >50 genes. Targeted gene panel testing with nexrt generation sequencing (NGS) is required for patients without typical phenotypic findings. The aim was to determine the genetic etiologies of patients with IHH using NGS, including 54 IHH-associated genes, and to present protein homology modeling and protein stability analyzes of the detected variations.Methods: Clinical and demographic data of 16 patients (eight female), aged between 11.6-17.8 years, from different families were assessed. All patients were followed up for a diagnosis of nIHH, had normal cranial imaging, were without anterior pituitary hormone deficiency other than gonadotropins, had no sex chromosome anomaly, had no additional disease, and underwent genetic analysis with NGS between the years 2008-2021. Rare variants were classified according to the variant interpretation framework of the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology. Changes in protein structure caused by variations were modeled using RoseTTAFold and changes in protein stability resulting from variation were analyzed.Results: Half of the 16 had no detectable variation. Three (18.75%) had a homozygous (pathogenic) variant in the GNRHR gene, one (6.25%) had a compound heterozygous [likely pathogenic-variants of uncertain significance (VUS)] variant in PROK2 and four (25%) each had a heterozygous (VUS) variant in HESX1, FGF8, FLRT3 and DMXL2. Protein models showed that variants interpreted as VUS according to ACMG could account for the clinical IHH.Conclusion: The frequency of variation detection was similar to the literature. Modelling showed that the variant in five different genes, interpreted as VUS according to ACMG, could explain the clinical IHH.Öğe Clinical Characteristics and Genetic Analyses of Patients with Idiopathic Hypogonadotropic Hypogonadism (vol 15, pg 160, 2023)(Galenos Publ House, 2023) Ciftci, Nurdan; Akinci, Aysehan; Akbulut, Ekrem; Camtosun, Emine; Dundar, Ismail; Dogan, Mustafa; Kayas, Leman[Abstract Not Available]Öğe Delineating the Adult Phenotype of PGM2L1-Related Neurodevelopmental Disorder(Wiley, 2026) Ercoskun, Pelin; Akbulut, Ekrem; Yavas, Cuneyd; Yilmaz Celik, Lale; Dogan, MustafaPGM2L1 is a crucial enzyme exhibiting glucose 1,6-bisphosphate synthase activity, with predominant expression in brain tissue. In 2021, biallelic pathogenic variants in the PGM2L1 gene were first linked to a neurodevelopmental disorder characterized primarily by developmental delay in four pediatric cases. In this study, we aimed to delineate the adult phenotype associated with the PGM2L1-related neurodevelopmental disorder and to perform functional characterization of the identified variant. Two siblings presenting with neurodevelopmental delay were evaluated clinically and genetically. Exome sequencing of the older sibling revealed a homozygous nonsense variant, c.277C>T p.(Gln73Ter), in the PGM2L1 gene. This variant results in truncation leading to loss of key functional domains including the substrate binding site, catalytic active site, and protein stability regions. Quantitative analysis demonstrated a significant reduction in PGM2L1 gene expression in both siblings compared to controls (p value < 0.01). Unlike previously reported pediatric cases, the second sibling exhibited additional features including scoliosis, renal anomaly, tooth loss, hypothyroidism, bladder trabeculation, anhidrosis, and temperature intolerance, notably in the absence of obesity. These cases represent the first detailed description of an adult phenotype associated with a biallelic pathogenic variant in PGM2L1, expanding the clinical spectrum of this neurodevelopmental disorder.Öğe Demographic, Sociocultural, and Time-Related Patterns of Violent Suicide Attempts(Int Scientific Information, Inc, 2025) Cumaoglu, Mustafa Oguz; Vural, Abdussamed; Dolanbay, Turgut; Dogan, Mustafa; Sekme, SabriBackground: Violent suicide attempts (VSAs), characterized by high-lethality methods such as hanging, firearms, and sharpobject injuries, are a significant public health concern. While VSAs are widespread globally, research on their associated factors remains limited. This study investigated demographic, sociocultural, and environmental factors influencing VSAs in Turkey's southern region, emphasizing time-related and seasonal patterns, to guide public health strategies. Material/Methods: Data were retrospectively collected from 86 VSA patients admitted to Nigde University Hospital between January 1 and December 31, 2023. Parameters assessed included demographics, marital status, education, psychiatric history, suicide methods, time of day, weekday trends, and seasonal environmental factors like temperature, precipitation, and wind speed. Statistical analyses revealed meaningful associations between sociodemographic characteristics, clinical features, and environmental factors and patterns of violent suicide attempts. Results: VSAs were more frequent among men, single people, and divorced individuals. Gender differences emerged in suicide methods: men predominantly used hanging and firearms, while women favored sharp objects. Psychiatric disorders were significantly less common among married individuals compared to single people and divorcees. VSAs were more prevalent on weekdays, peaking in the morning, with fatality rates highest in the afternoon. Seasonal analysis revealed spring as the peak period for VSAs, correlated with higher precipitation and wind speeds. Conclusions: The findings show the role of demographic, psychiatric, and environmental factors in VSA patterns. High-risk groups include single and divorced individuals and those with psychiatric disorders. Tailored interventions addressing seasonal and time-related patterns and enhancing support networks could mitigate VSA risks. Improved mental health services and targeted public health policies are essential for effective suicide prevention.Öğe Effect of adiponectin on a disintegrin and metalloproteinase with thrombospondin motifs-9 gene expression in human chondrocytes(Amer Assoc Immunologists, 2014) Yaykasli, Kursat; Dogan, Mustafa; Hatipoglu, Omer; Yaykasli, Emine; Kaya, Ertugrul; Ozsahin, Mustafa; Uslu, Mustafa[Abstract Not Available]Öğe Functional evaluation of NAA10 variants in patients with Ogden syndrome(Lippincott Williams & Wilkins, 2026) Aydin Gumus, Aydeniz; Dogan, Mustafa; Gezdirici, Alper; Akbulut, Ekrem; Kinay Ermis, DuyguObjectives The catalytic subunit of NatA, the main component of the N-terminal acetyltransferase complex, which is involved in most of the acetylation of the human proteome, is encoded by the NAA10 gene. Mutations in the NAA10 gene lead to neurodegenerative diseases associated with disruption of acetylation. Ogden syndrome (OS) is a rare X-linked recessive or dominantly inherited disorder associated with NAA10 gene mutations, characterized by variable findings such as autism spectrum disorder, intellectual disability, and cardiac anomalies. In this article, it is aimed to clarify the functionality of two novel NAA10 gene variants in two female patients with OS. Methods A whole-exome sequencing (WES) study was performed from the blood samples of the patients. The effects of the two variants found by tertiary structure modeling, protein stability analysis, and molecular docking analyses on NAA10 were examined. Results Autism, intellectual retardation, and epilepsy were prominent in the patients, and heterozygous variants c.346C>T and c.439A>T in the NAA10 gene were detected in WES. The clinical findings were compatible with OS. The p.Arg116Trp and p.Met147Leu changes in the NAA10 gene caused changes in the overall topological structure of NAA10, including the substrate and ligand binding site. Conclusion In this study, c.346C>T and c.439A>T variants were found to alter the functional stability, structure, and energy of NAA10. Functional analyses of NAA10 variants in two rare OS patients have once again demonstrated that novel variants are essential studies for phenotype-genotype correlation association steps.Öğe Leptin induction of aggrecanases-1 and-2 genes expression in human chondrocytes is mediated by p38 mitogen-activated protein kinase pathway(Amer Assoc Immunologists, 2014) Hatipoglu, Omer; Yaykasli, Kursat; Dogan, Mustafa; Yaykasli, Emine; Kaya, Ertugrul; Ozsahin, Mustafa; Usiu, Mustafa[Abstract Not Available]Öğe NF-?B and MAPKs are involved in resistin-caused ADAMTS-5 induction in human chondrocytes(Canadian Soc Clinical Investigation, 2015) Hatipoglu, Omer F.; Yaykasli, Kursat O.; Dogan, Mustafa; Yaykasli, Emine; Bender, Onur; Yasar, Tugce; Tapan, SafaPurpose: Chronic inflammation is an important etiological factor in the development of arthritic diseases. Several factors contribute to aggregation of chronic inflammation, including the presence of excess adipose tissue. Methods: The putative induction mechanisms of ADAMTS-5 by resistin were investigated in normal primary human articular chondrocytes. Expression levels of the ADAMTS-5 gene were determined at several resistin doses and durations. Results: Human chondrocytes were activated and associated with upregulated ADAMTS-5 gene expression after exposure to resistin (also known as adipose tissue-specific secretary factor, ADSF). Release of ADAMTS-5 leads to joint cartilage degradation, a key event in the development of arthritic diseases rheumatoid arthritis (RA) and osteoarthritis (OA). Activation of chondrocytes was associated with upregulated NF-kappa B protein levels in a time-dependent fashion. Co-incubation of human chondrocytes with JNK and p38 inhibitors lead to abrogated levels of NF-kappa B, indicating that these MAPKs are important in the activation of chondrocytes after stimulation with resistin. Similarly, ADAMTS-5 expression levels were abrogated when co-incubated with p38, NF-kappa B, JNK, MEK and PI3K inhibitors. Our results demonstrate that resistin, released from adipose tissue, may be involved in the development of RA and OA in obese patients through degradation of joint cartilage via ADAMTS-5 released from activated chondrocytes.Öğe Novel biallelic nonsense mutation in IGHMBP2 gene linked to neuropathy (CMT2S): A comprehensive clinical, genetic and bioinformatic analysis of a Turkish patient with literature review(Elsevier, 2025) Yavas, Cuneyd; Dogan, Mustafa; Ozgor, Bilge; Akbulut, Ekrem; Eroz, RecepBackground: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth type 2S (CMT2S) typically present before age 10. Genetic factors account for up to 50 % of neuropathies, which often display varied symptoms. Mutations in the IGHMBP2 gene are associated with both CMT2S and SMARD1, resulting in a rare clinical condition marked by axonal neuropathy, spinal muscular atrophy, respiratory distress, and muscle weakness. Method: Detailed family histories and medical data were collected. Segregation analysis was performed using Sanger sequencing and whole exome sequencing. Additionally, a review of molecularly confirmed patients was conducted. Protein tertiary structures expressed in the IGHMBP2 gene were tested for topological and conformational changes using modeling programs and in-silico tools. Results: We identified a novel homozygous nonsense mutation (c.2568_2569del p.Gly857Alafs*27) in a family with a member showing neuropathy. This report details the clinical and genetic findings of the affected individuals, including a Turkish patient with neuropathy, and compares them with literature cases. Conclusion: Understanding the clinical impact of the (c.2568_2569del p.Gly857Alafs*27) mutation will enhance our knowledge of IGHMBP2 gene defects role in neuropathy. This study aims to highlight this severe recessive disease caused by pathogenic IGHMBP2 gene mutations and to examine the mutation spectrum and phenotype differences.Öğe Visfatin increases the activity of aggrecanases-1 and-2 in human chondrocytes(Amer Assoc Immunologists, 2014) Yaykasli, Kursat; Dogan, Mustafa; Hatipoglu, Omer; Yaykasli, Emine; Kaya, Ertugrul; Ozsahin, Mustafa; Uslu, Mustafa[Abstract Not Available]
