A. Nazlı Başak
A5002736771- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Hereditary Neurological Disorders
- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- Nutrition, Genetics, and Disease
- Hemoglobinopathies and Related Disorders
- Alzheimer's disease research and treatments
- Neurological disorders and treatments
- Genomic variations and chromosomal abnormalities
- Iron Metabolism and Disorders
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Nuclear Receptors and Signaling
- Genetic Associations and Epidemiology
- Botulinum Toxin and Related Neurological Disorders
- Muscle Physiology and Disorders
- Biochemical Acid Research Studies
- Cancer-related gene regulation
- Fetal and Pediatric Neurological Disorders
- Myasthenia Gravis and Thymoma
- DNA Repair Mechanisms
Koç University
2019-2025
Boğaziçi University
2011-2021
Neurology, Inc
2021
Istanbul University
2015
Sakarya University
2015
University of Copenhagen
2012
Translational Genomics Research Institute
2010
Tokat Gaziosmanpaşa Üniversitesi
2009
Athens State University
2009
Hippocration General Hospital
2009
Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age symptom onset less than 25 years and variable presentation.
The construction of population-based variomes has contributed substantially to our understanding the genetic basis human inherited disease. Here, we investigated structure Turkey from 3,362 unrelated subjects whose whole exomes (n = 2,589) or genomes 773) were sequenced generate a Turkish (TR) Variome that should serve facilitate disease gene discovery in Turkey. Consistent with history present-day as crossroads between Europe and Asia, found extensive admixture Balkan, Caucasus, Middle...
Pathogenic variants in PRKN cause early‐onset Parkinson's disease (PD), while the role of alpha‐synuclein ‐PD remains uncertain. One study performed a blood‐based seed amplification assay (SAA) ‐PD, not detecting 17 patients. By applying methodologically different SAA focusing on neuron‐derived extracellular vesicles, we demonstrated 8 13 patients, challenging view as non‐synucleinopathy. Moreover, blinded replication vesicles‐dependent idiopathic PD patients and healthy controls. In...
Background Despite several studies suggesting a potential oligogenic risk model in amyotrophic lateral sclerosis (ALS), case–control statistical evidence implicating oligogenicity with disease or clinical outcomes is limited. Considering its direct and therapeutic implications, we aim to perform large-scale robust investigation of ALS the course. Methods We leveraged Project MinE genome sequencing datasets (6711 cases 2391 controls) identify associations between known genes risk, as well...
The biological basis for the development of cerebro-cerebellar structures required posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, hypoplasia, linked to 7.1-Mb region homozygosity on chromosome 17p13.1–13.3. Diffusion weighted imaging fiber tractography patients' brains revealed morphological abnormalities cerebellum corpus callosum,...
To foster trial-readiness of coenzyme Q8A (COQ8A)-ataxia, we map the clinicogenetic, molecular, and neuroimaging spectrum COQ8A-ataxia in a large worldwide cohort, provide first progression data, including treatment response to Q10 (CoQ10).Cross-modal analysis multicenter cohort 59 COQ8A patients, genotype-phenotype correlations, 3D-protein modeling, vitro mutation analyses, magnetic resonance imaging (MRI) markers, disease progression, CoQ10 data.Fifty-nine patients (39 novel) with 44...
Abstract Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies vacuolar sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation macromolecules organelles are linked to human disease. VPS proteins function as part complexes such the homotypic fusion vacuole (HOPS) tethering composed VPS11, VPS16, VPS18, VPS33A, VPS39 VPS41. The HOPS-specific subunit VPS41 has been reported...
Genetics, pathology, and molecular studies demonstrate that microRNA-218 is modulated might play a role in amyotrophic lateral sclerosis.
Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified families with autosomal dominant Parkinson's disease (PD) and sporadic cases; G2019S mutation is single most frequent. Intriguingly, frequency of this PD patients varies greatly among ethnic groups geographic origins: it present at <0.1% East Asia, ∼2% European-descent can reach frequencies up to 15–40% Ashkenazi Jews North African Arabs. To ascertain evolutionary dynamics different populations, we genotyped 74...
A reason for screening amyotrophic lateral sclerosis (ALS) patients mutations in the superoxide dismutase-1 (SOD1) gene is opportunity to find novel with properties that can give information on pathogenesis. c.352C>G (L117V) SOD1 mutation was found two Syrian ALS families living Europe. The disease showed unusually low penetrance and slow progression. In erythrocytes, total activity, as well specific activity of mutant protein, equal carriers family controls lacking mutations. structural...
Expansions of the polyglutamine (polyQ) domain (≥34) in Ataxin-2 (ATXN2) are primary cause spinocerebellar ataxia type 2 (SCA2). Recent studies reported that intermediate-length (27–33) expansions increase risk Amyotrophic Lateral Sclerosis (ALS) 1–4% cases diverse populations. This study investigates Turkish population with respect to ALS risk, genotyping 158 sporadic, 78 familial patients and 420 neurologically healthy controls. We re-assessed effect ATXN2 extended analysis for first time...
Schizophrenia is one of the most common and complex neuropsychiatric disorders, which contributed both by genetic environmental exposures. Recently, it shown that NRG1-mediated ErbB4 signalling regulates many important cellular molecular processes such as growth, differentiation death, particularly in myelin-producing cells, glia neurons. Recent association studies have revealed genomic regions NRG1 ERBB4, are significantly associated with risk developing schizophrenia; however,...
ABSTRACT Background Pathogenic variants in SPTAN1 have been linked to a remarkably broad phenotypical spectrum. Clinical presentations include epileptic syndromes, intellectual disability, and hereditary motor neuropathy. Objectives We investigated the role of rare neurological disorders such as ataxia spastic paraplegia. Methods screened 10,000 NGS datasets across two international consortia one local database, indicative level collaboration currently required identify genes causative for...
Biallelic loss-of-function mutations in the sorbitol dehydrogenase (SORD) gene cause most common recessive type of Charcot-Marie-Tooth disease (CMT), CMT-SORD. However, full genotype-phenotype spectrum and progression remain to be defined. Notably, a multicenter phase 2/3 study test efficacy govorestat (NCT05397665), new aldose reductase inhibitor, is currently ongoing. Diagnosing CMT-SORD will become imperative when disease-modifying therapies available. In this cross-sectional multicentre...
Superoxide dismutase 1 (SOD1) is a crucial enzyme that protects cells from oxidative damage by converting superoxide radicals into H2O2 and O2. This detoxification process, essential for cellular homeostasis, relies on precisely orchestrated catalytic mechanism involving the copper cation, while zinc cation contributes to structural integrity of enzyme. study presents 2.3 Å crystal structure human SOD1 (PDB ID: 9IYK), revealing an assembly six homodimers twelve distinct active sites. The...
<title>Abstract</title> Background Inherited burden for disease predisposition in diverse populations is an open question. American College of Medical Genetics and Genomics (ACMG) guidelines variant classification, combined with large population variation databases, promise to provide valuable answers. We recently developed a robust ACMG-based automated classification tool categorized the exome sequencing variants 730,947 individuals from gnomAD. Methods leveraged allele frequency...