Yazar "Köse, Melis" seçeneğine göre listele

Listeleniyor 1 - 7 / 7
  • Küçük Resim Yok
    Öğe
    Clinical and Molecular Features of Our Pompe Patients: Single-Center Experience
    (2020) Köse, Melis; Köse, Engin; Kağnıcı, Mehtap; Ünalp, Aycan; Yılmaz, Ünsal; Yılmazer, Murat Muhtar; Edizer, Selvinaz
    Introduction: Pompe disease (PD), glycogen storage disease Type II (GSD II), is an autosomal recessive inherited lysosomal storage disease caused by pathogenic variants in the GAA gene that encodes lysosomal acid ?-glucosidadase (GAA) enzyme. the incidence of the disease varies from country to country. PD is mainly presents as two groups of phenotypes as infantile-onset Pompe disease (IOPD) and late-onset Pompe disease. Objective: the aim of this study is to discuss the molecular and clinical characteristics of infantile-onset Pompe disease (IOPD) and late-onset pompe disease (LOPD) followed-up in our center. Method: A total of 10 patients diagnosed with IOPD and 4 patients diagnosed with LOPD in Izmir Dr. Behcet Uz Pediatric Health and Diseases and Surgery Training and Research Hospital Pediatric Metabolism Unit between 06.01.2015 and 06.01. 2019 were included in the study. the patients’ demographic characteristics, clinical findings at the time of diagnosis and during the folllow-up period, biochemical findings, muscle biopsy data, results of enzymatic analyses and moleculargenetic characteristics were recorded retrospectively. Results: A total of 10 patients were included in the study. 7 patients were diagnosed with IOPD and 3 patients with LOPD. the median follow-up period of all patients was 26 months (range: 6-42 months). the c.896 C> T (8/32, 25%) is detected as the most common variant. 1237G>T (p.Asp413Tyr), c.2019 C>A (p.Asn673Lys), c.418A>T (p.Asn140Tyr) variants were detected for the first time. Conclusion: Pompe disease is one of the most important congenital metabolic diseases in which early diagnosis and treatment are of great importance. Despite the significant improvement in disease prognosis with the introduction of enzyme replacement therapy, there are still patients with poor prognosis despite early diagnosis. Phenotype-genotype studies are crucial in this respect.
  • Küçük Resim Yok
    Öğe
    Clinical and Molecular Features of Our Pompe Patients: Single-Center Experience
    (2020) Onay, Hüseyin; Yıldırım, Eser Sözmen; Gürsoy, Semra; Kağnıcı, Mehtap; Köse, Melis; Köse, Engin; Yılmaz, Ünsal
    Introduction: Pompe disease (PD), glycogen storage disease Type II (GSD II), is an autosomal recessive inherited lysosomal storage disease caused by pathogenicvariants in the GAA gene that encodes lysosomal acid ?-glucosidadase (GAA) enzyme. The incidence of the disease varies from country to country. PD is mainlypresents as two groups of phenotypes as infantile-onset Pompe disease (IOPD) and late-onset Pompe disease.Objective: The aim of this study is to discuss the molecular and clinical characteristics of infantile-onset Pompe disease (IOPD) and late-onset pompe disease(LOPD) followed-up in our center.Method: A total of 10 patients diagnosed with IOPD and 4 patients diagnosed with LOPD in Izmir Dr. Behcet Uz Pediatric Health and Diseases and Surgery Trainingand Research Hospital Pediatric Metabolism Unit between 06.01.2015 and 06.01. 2019 were included in the study. The patients’ demographic characteristics,clinical findings at the time of diagnosis and during the folllow-up period, biochemical findings, muscle biopsy data, results of enzymatic analyses and moleculargenetic characteristics were recorded retrospectively.Results: A total of 10 patients were included in the study. 7 patients were diagnosed with IOPD and 3 patients with LOPD. The median follow-up period of allpatients was 26 months (range: 6-42 months). The c.896 C> T (8/32, 25%) is detected as the most common variant. 1237G>T (p.Asp413Tyr), c.2019 C>A(p.Asn673Lys), c.418A>T (p.Asn140Tyr) variants were detected for the first time.Conclusion: Pompe disease is one of the most important congenital metabolic diseases in which early diagnosis and treatment are of great importance. Despitethe significant improvement in disease prognosis with the introduction of enzyme replacement therapy, there are still patients with poor prognosis despite earlydiagnosis. Phenotype-genotype studies are crucial in this respect.
  • Küçük Resim Yok
    Öğe
    Clinical, Neuroimaging, and Genetic Features of the Patients with L-2-Hydroxyglutaric Aciduria
    (2018) Canda, Ebru; Köse, Melis; Yazıcı, Havva; Er, Esra; Eraslan, Cenk; Uçar, Sema Kalkan; Karaca, Emin
    Aim: L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive encephalopathy caused by mutations in the L-2-hydroxyglutarate dehydrogenase gene. Materials and Methods: Here we discuss the clinical and molecular characteristics in patients with L2HGA. Results: There were eight patients with L2HGA. Their median age was 16 (9.5-37) years. Five of them were female and three of them were male. the main symptoms of the patients were psychomotor retardation (8/8), cerebellar ataxia (5/8), extrapyramidal symptoms (7/8) and seizures (4/8). All patients had behavioral problems. Elevated urinary L-2-hydroxy (L-2-OH) glutaric acid was detected and the median level of urine L-2-OH glutaric acid at diagnosis was 146 (60-1460 nmol/mol creat). Characteristic magnetic resonance imaging findings including subcortical cerebral white matter abnormalities with T2 hyperintensities of the dentate nucleus, globus pallidus and putamen were detected. Two patients had homozygous R335X, two patients had homozygous R282Q, two patients had homozygous R302L and one patient had compound heterozygous P302L/A64T mutation in L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene. Conclusion: Because of the slow progression of the disease, the diagnosis of the patients is usually belated. L2HGA must be considered in the differential diagnosis based on clinical findings and specific findings in cranial magnetic resonance imaging. in our study, one of our patients has a novel mutation.
  • Küçük Resim Yok
    Öğe
    Congenital Disorder of Glycosylation: Clinical andMolecular Characteristics of 9 Patients from Turkey
    (2020) Özdemir, Taha Reşid; Köse, Engin; Köse, Melis; Yılmaz, Ünsal; Ünalp, Aycan; Onay, Hüseyin; Tekin, Hande Gazateci
    Objective: Congenital defects of glycosylation (CDG) belongs to a group of genetic diseases that lead to impairment in protein, lipid glycosylation and glycosylphosphatidylinositol synthesis. More than 140 types of CDG have been identified and the number is increasing day by day. Since glycosylation is very important for post-translational process and glycosylation is required for half of the proteins in human organism to be able to exert an effect, causes the disease to have an extremely wide clinical spectrum in affected patients. Our aim is to share the clinical features of our patients with CDG and contribute to increase in the awareness of this disease group with highly heterogeneous clinical spectrum.Method: Nine patients from 9 families whose molecular and biochemical diagnosis was confirmed were included in the study. All patients were evaluated by a specialist.in pediatric metabolism Laboratory analysis results and clinical features were obtained from hospital records. Our study presents clinical, biochemical and molecular properties of 9 patients. Results: The patients were detected as having PMM2-CDG (CDG Ia) (n=4), MPI-CDG (CDG Ib) (n=1), ALG3-CDG (CDG Id) (n=1), ALG1-CDG (CDG Ik) (n=1), DOLK-CDG (CDG Im) (n=1) and COG4-CDG (CDG IIj) (n=1). Sialotransferrin electrophoresis could be performed in 8 of 9 patients. Six patients were diagnosed using high- throughout next -generation sequencing technologies. In all of our patients previously indentified variants have been detected. Conclusion: Our study is one of the first CDG case series presented in our country. CDG should be kept in mind as an important preliminary diagnosis in patients with multisystemic involvement and neurological findings.
  • Küçük Resim Yok
    Öğe
    Evaluation of Cardiovascular Involvement and Cytokine Levels in Patients with Mucopolysaccharidosis
    (2019) Canda, Ebru; Köse, Melis; Kağnıcı, Mehtap; Dondurmacı, Meral; Uçar, Sema Kalkan; Sözmen, Eser; Çoker, Mahmut
    Aim: Cardiovascular involvement is common in patients with mucopolysaccharidoses (MPS). in this study, we investigated the effects of the markers involved in vascular endothelial injury pathogenesis [transforming growth factor ?- (TGF-?)], interleukin-6 (IL-6), IL-10, high sensitive-C reactive protein (hs-CRP), vascular endothelial growth factor (VEGF), N-terminal pro-Natriuretic peptide (NT-proBNP) and the clinical, laboratory and echocardiographic findings of the patients. Materials and Methods: A total of 37 patients (5 MPS I, 4 MPS II, 2 MPS IIIa, 4 MPS IIIb, 14 MPS IVa, 8 MPS VI) and 32 controls with similar age and sex were included in the study. Results: Corneal clouding was seen in 29 (78%) patients. There were 23 (62%) patients with organomegaly, and 28 (75%) patients with hearing loss. When the groups were compared in terms of NT-proBNP, hs-CRP, TGF-?, IL-6, IL-10 and VEGF levels, there was a statistically significant increase in the patient group for NT-proBNP and VEGF (p=0.04, p=0.03, respectively). the carotid intima media thickness was statistically significantly higher in the patient group (p<0.001). the left ventricular diastolic diameter was significantly higher in the patient group (p=0.009), intraventricular septum thickness was significantly higher in the patient group (p<0.001). the E/A ratio was significantly lower in the patient group (p<0.001). Conclusion: Cardiac involvement in MPS patients is a major cause of mortality and morbidity. It is thought that cytokines, proinflammatory markers are elevated in patients with vascular damage like other lysosomal diseases. There is a need for further studies to determine biomarkers for vascular involvement.
  • Küçük Resim Yok
    Öğe
    Evaluation of Cardiovascular Involvement and Cytokine Levels in Patients with Mucopolysaccharidosis
    (2019) Canda, Ebru; Köse, Melis; Kağnıcı, Mehtap; Dondurmacı, Meral; Uçar, Sema Kalkan; Sözmen, Eser; Çoker, Mahmut
    Aim: Cardiovascular involvement is common in patients with mucopolysaccharidoses (MPS). In this study, we investigated the effects of the markers involved in vascular endothelial injury pathogenesis [transforming growth factor ?- (TGF-?)], interleukin-6 (IL-6), IL-10, high sensitive-C reactive protein (hs-CRP), vascular endothelial growth factor (VEGF), N-terminal pro-Natriuretic peptide (NT-proBNP) and the clinical, laboratory and echocardiographic findings of the patients. Materials and Methods: A total of 37 patients (5 MPS I, 4 MPS II, 2 MPS IIIa, 4 MPS IIIb, 14 MPS IVa, 8 MPS VI) and 32 controls with similar age and sex were included in the study. Results: Corneal clouding was seen in 29 (78%) patients. There were 23 (62%) patients with organomegaly, and 28 (75%) patients with hearing loss. When the groups were compared in terms of NT-proBNP, hs-CRP, TGF-?, IL-6, IL-10 and VEGF levels, there was a statistically significant increase in the patient group for NT-proBNP and VEGF (p=0.04, p=0.03, respectively). The carotid intima media thickness was statistically significantly higher in the patient group (p<0.001). The left ventricular diastolic diameter was significantly higher in the patient group (p=0.009), intraventricular septum thickness was significantly higher in the patient group (p<0.001). The E/A ratio was significantly lower in the patient group (p<0.001). Conclusion: Cardiac involvement in MPS patients is a major cause of mortality and morbidity. It is thought that cytokines, proinflammatory markers are elevated in patients with vascular damage like other lysosomal diseases. There is a need for further studies to determine biomarkers for vascular involvement.
  • Küçük Resim Yok
    Öğe
    Mitokondriyal hastalık öntanılı hastalarda tüm ekzom dizi analizi ile moleküler genetik tanının araştırılması ve sorumlu yeni genlerin keşfi
    (Ege Üniversitesi, 2023) Köse, Melis; Özkinay, Feriştah Ferda; Atik, Tahir
    Giriş: Mitokondriyal hastalıklar (MH), temelde elektron transport zinciri (ETZ) fonksiyon bozukluğuna yol açan hastalıklardır. Sıklığının 1.6/5000 olduğu tahmin edilmektedir ve en sık kalıtımsal nörometabolik hastalık grubudur. Mitkondriyal proteomun 100 civarında proteini direk olarak ETZ ilişkilidir. 300'den fazla nükleer gen defektinin MH'a yol açtığı bilinmektedir. Günümüze kadar edindiğimiz bilgiler ile genotip-fenotip uyumundan sözetmek mümkün değildir. Çalışmamız, mitokondriyal hastalıklarda tanı başarısını arttırmaya yönelik olarak yeni nesil dizi analizi yöntemleri ile fonksiyonel doku analizlerini aynı basamakta birleştirerek tanı başarısını arttırmayı amaçlamaktadır. Yöntem: Ege Üniversitesi Tıp Fakültesi Çocuk Genetik Bilim Dalında mitokondriyal hastalık ön tanısı ile takip edilen, aynı ailede birden fazla etkilenmiş birey olan ve aile ağacı otozomal resesif kalıtım ile uyumlu olan, öncesinde mitokondriyal DNA analizi ve mitokondriyal DNA MLPA analizi ile mitokondriyal DNA ilişkili mitokondriyal hastalıklar dışlanmış olan ancak klinik ve laboratuar bulgular ile (klinik ve laboratuvar) spesifik bir tanı oluşturulamamış olan yaşları 0-18 yaş arasında olan 20 indeks vakaya WES analizi ve eş zamanlı olarak doku örneklemleri alınarak kompleksomik analizi yapılmıştır. Bulgular: Örneklem grubumuzda 10 hastada moleküler ve biyokimyasal olarak tanı konmuştur. Hastalarımızda RRM2B, MTO1, MPV17, NAR2, SDHAF1, COX5A , COQ4, C12Orf65, PDHA1, NDUFAF6 genlerinde toplam 11 varyant saptanmıştır. Saptanan varyantlardan 7/11 varyant ilk kez tanımlanmış, 4/11 varyant daha önce tanımlı varyantlar olarak değerlendirilmiştir. 5/11 varyant missense, 1/11 çerçeve kayması, 2/11 nonsense, 2/11 başlangıç kodonu kaybına neden olan varyantlar olarak saptanmıştır. Kompleksomik analizleri değerlendirildiğinde 7/11 hastada kombine oksidatif fosforilasyon edefekti, 2/11 hastada izole kompleks eksikliği, 2/11 hastada normal olarak saptandı. Bir hastada dokuda kurtarma çalışması yapılarak tanı doğrulaması gerçekleştirildi. Sonuç: Bu çalışmada WES daha önce mtDNA analizi ve konvansiyonel metabolik tarama testleri ile tanı alamamış olan 10 hastanın moleküler etyolojisi belirlendi. MH grubunda yeni nesil dizi analizi yöntemlerinin fonksiyonel analizlerle desteklenmesinin tanı başarısını arttırdığı görülmüştür.