Hande Caglayan

Hande Caglayan
Bogazici University · Department of Molecular Biology and Genetics

PhD

About

78
Publications
14,487
Reads
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2,451
Citations
Citations since 2016
24 Research Items
1751 Citations
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
2016201720182019202020212022050100150200250300
Additional affiliations
January 2013 - March 2015
Bogazici University
Position
  • Head of Department
January 1997 - February 2016
Bogazici University
Position
  • Professor (Full)

Publications

Publications (78)
Preprint
Full-text available
Objective: De novo missense variants in KCNQ5, encoding the voltage–gated K+ channel KV7.5, have been described as a cause of developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease–related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms. Methods: 1292 fam...
Article
Full-text available
SCN4A gene mutations cause a number of neuromuscular phenotypes including myotonia. A subset of infants with myotonia‐causing mutations experience severe life‐threatening episodic laryngospasm with apnea. We have recently identified similar SCN4A mutations in association with sudden infant death syndrome. Laryngospasm has also been proposed as a co...
Article
The developmental and epileptic encephalopathies (DEEs) are heterogeneous disorders with a strong genetic contribution, but the underlying genetic etiology remains unknown in a significant proportion of individuals. To explore whether statistical support for genetic etiologies can be generated on the basis of phenotypic features, we analyzed whole-...
Article
Juvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain‐containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island...
Article
Full-text available
Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies characterized by refractory seizures and developmental impairment. Sequencing approaches have identified causal genetic variants in only about 50% of individuals with DEEs.1–3 This suggests that unknown genetic etiologies exist, potentially in the ∼98% of human gen...
Article
Full-text available
Background Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy.
Article
BACKGROUND: Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy. METHODS: For this exome-based case-control study, we used...
Article
Full-text available
Epilepsy is a frequent feature of neurodevelopmental disorders (NDDs), but little is known about genetic differences between NDDs with and without epilepsy. We analyzed de novo variants (DNVs) in 6,753 parent–offspring trios ascertained to have different NDDs. In the subset of 1,942 individuals with NDDs with epilepsy, we identified 33 genes with a...
Preprint
Epilepsy is a frequent feature of neurodevelopmental disorders (NDD) but little is known about genetic differences between NDD with and without epilepsy. We analyzed de novo variants (DNV) in 6753 parent-offspring trios ascertained for different NDD. In the subset of 1942 individuals with NDD with epilepsy, we identified 33 genes with a significant...
Article
Full-text available
Recently, de novo mutations in the gene KCNA2, causing either a dominant-negative loss-of-function or a gain-of-function of the voltage-gated K⁺ channel Kv1.2, were described to cause a new molecular entity within the epileptic encephalopathies. Here, we report a cohort of 23 patients (eight previously described) with epileptic encephalopathy carry...
Article
Importance Knowing the range of symptoms seen in patients with a missense or loss-of-function variant in KCNB1 and how these symptoms correlate with the type of variant will help clinicians with diagnosis and prognosis when treating new patients. Objectives To investigate the clinical spectrum associated with KCNB1 variants and the genotype-phenot...
Article
The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox–Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients with IS or LGS. The contribution of autosomal recessi...
Article
The 8p23.1 deletion syndrome is a rare multisystem disorder with high penetrance and a variable phenotypic spectrum that includes congenital heart disease (CHD), intellectual disability, behavioural problems, microcephalia, and sometimes epilepsy. Genomic copy number variations (CNVs) constitute an important genetic risk factor for common genetic g...
Article
Full-text available
Benign familial infantile epilepsy (BFIE) is clinically characterized by clusters of brief partial seizures progressing to secondarily generalized seizures with onset at the age of 3-7 months and with favorable outcome. PRRT2 mutations are the most common cause of BFIE, and found in about 80% of BFIE families. In this study, we analyzed a large mul...
Article
© 2017(The American Journal of Human Genetics 95, 360–370; October 2, 2014) In the list of consortium members for the Epilepsy Phenome/Genome Project, member Dina Amrom's name was misspelled as Amron. The authors regret the error.
Article
We report a de novo SMARCA2 missense mutation discovered on exome sequencing in a patient with myoclonic astatic epilepsy, leading to reassessment and identification of Nicolaides–Baraitser syndrome. This de novo SMARCA2 missense mutation c.3721C>G, p.Gln1241Glu is the only reported mutation on exon 26 outside the ATPase domain of SMARCA2 to be ass...
Article
Full-text available
Objective: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. Methods: Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using th...
Article
Full-text available
Background: Abnormalities in the biosynthetic pathway or increased clearance of plasma von Willebrand factor (VWF) are likely to contribute to decreased plasma VWF levels in inherited type 1 von Willebrand disease (VWD). Recent studies demonstrated that 65% of type 1 VWD patients have candidate VWF mutations, the majority of which are missense var...
Article
Full-text available
Purpose: The SCN1A gene is one of the most commonly mutated human epilepsy genes associated with a spectrum of phenotypes with variable degrees of severity. Despite over 1200 distinct mutations reported, it is still hard to draw clear genotype-phenotype relationships, since genetic and environmental modifiers contribute to the development of a par...
Article
Full-text available
Objective: We aimed to delineate the neurodevelopmental spectrum associated with SYNGAP1 mutations and to investigate genotype-phenotype correlations. Methods: We sequenced the exome or screened the exons of SYNGAP1 in a total of 251 patients with neurodevelopmental disorders. Molecular and clinical data from patients with SYNGAP1 mutations from...
Article
Full-text available
Background: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what exten...
Article
Full-text available
Late-onset myoclonic epilepsy is being increasingly recognized as a late complication in elderly patients with Down syndrome (DS) in association with cognitive decline. This specific syndrome bears some broad clinical and EEG similarities to the progressive myoclonic epilepsies, particularly Unverricht-Lundborg disease (ULD). Our aim was to investi...
Article
Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features 1–6. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel K V 1.2, in six isolated patients with ep...
Article
Full-text available
Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six isolated patients with epilepti...
Article
Full-text available
Dravet syndrome (DS) is a severe epilepsy syndrome starting in infantile period and caused usually by mutations of SCN1A gene. SUDEP (sudden unexplained death in epilepsy) is described as death in epilepsy patients with unknown reason even after postmortem examinations. DS is associated with a higher risk of SUDEP. A 20-year-old man had experienced...
Article
Full-text available
zet Dravet sendromu (DS) genellikle SCN1A genindeki mutasyonlara bağlı gelişen, infantil dönemde başlayan kötü seyirli bir epilepsi sendromudur. SUDEP (Sudden unexplained death in epilepsy) epilepsi hastalarında ani, postmortem incelemenin ölümün nedenini ortaya çıkartamadığı ölüm olarak tanımlanmaktadır. DS olgularında SUDEP diğer epilepsi hastala...
Article
Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the “cl...
Article
Full-text available
Hyperpolarization-activated, cyclic nucleotide–gated (HCN) channels contribute to cationic I h current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequ...
Conference Paper
Full-text available
Late-onset myoclonic epilepsy is being increasingly recognized as a late complication in elderly patients with Down syndrome (DS) in association with cognitive decline. This specific syndrome bears some broad clinical and EEG similarities to the progressive myoclonic epilepsies, particularly Unverricht-Lundborg disease (ULD). Our aim was to investi...
Article
Full-text available
Objective: A severe complication in the replacement therapy of hemophilia A (HA) patients is the development of alloantibodies (inhibitors) against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in t...
Article
Full-text available
Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the ''c...
Article
Dravet syndrome is a severe epilepsy syndrome characterized by infantile onset of therapy-resistant, fever-sensitive seizures followed by cognitive decline. Mutations in SCN1A explain about 75% of cases with Dravet syndrome; 90% of these mutations arise de novo. We studied a cohort of nine Dravet-syndrome-affected individuals without an SCN1A mutat...
Article
Dravet syndrome is a severe epilepsy syndrome characterized by infantile onset of therapy-resistant, fever-sensitive seizures followed by cognitive decline. Mutations in SCN1A explain about 75% of cases with Dravet syndrome; 90% of these mutations arise de novo. We studied a cohort of nine Dravet-syndrome-affected individuals without an SCN1A mutat...
Article
97 Von Willebrand Factor (VWF) is a multimeric glycoprotein that maintains hemostasis in the vascular system. VWF is secreted mainly from endothelial cells. During its biosynthesis VWF undergoes a series of post-translational modifications and some of the newly synthesized protein is released constitutively. The remainder of the protein is stored f...
Article
Full-text available
Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) in...
Article
Full-text available
An increasing number of mutations and polymorphisms have been identified in the von Willebrand factor (VWF) gene of patients with von Willebrand disease (VWD). Most of the sequence alterations are within exon 28, duplicated in the VWF pseudogene on chromosome 22. Genetic recombination causing the gene conversion between the VWF gene and its pseudog...
Article
Full-text available
Lafora disease is a rare, fatal, autosomal recessive progressive myoclonic epilepsy. The condition is characterised by seizures, myoclonus and dementia. In this case report, a patient who presented with generalised tonic-clonic seizures at the age of 30 is discussed. Until the age of 48, the patient did not have myoclonic jerks or ataxia clinically...
Article
Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% with heritability estimates of 80%. A considerable proportion of families with siblings affected by GGEs presumably display an oligogenic inheritance. The present genome-wide linkage meta-analysis aimed to map: (1) susceptibility loci shared by a broad spectrum of GGEs, and (2...
Article
Lafora disease (LD) is a type of autosomal recessive, progressive myoclonus epilepsy resulting mostly from mutations in the EPM2A and NHLRC1 genes. Mutational analysis in both genes was initiated with the aim of establishing LD DNA diagnosis in Turkey. Four novel NHLRC1 (p.G131X, p.P69S and p.D82H) and EPM2A (p.V7A) and two recurrent NHLRC1 (p.D146...
Article
Benign familial neonatal seizures (BFNS) are a dominant epilepsy syndrome caused by mutations in the voltage-gated potassium channels K(V) 7.2 and K(V) 7.3. We examined the molecular pathomechanism of a BFNS-causing mutation (p.N258S) in the extracellular S5-H5 loop of K(V) 7.2. Wild type (WT) and mutant channels, expressed in both Xenopus laevis o...
Article
Full-text available
To further evaluate the previously shown linkage of absence epilepsy (AE) to 2q36, both in human and WAG/Rij absence rat models, a 160-kb region at 2q36 containing eight genes with expressions in the brain was targeted in a case-control association study involving 205 Turkish patients with AE and 219 controls. Haplotype block and case-control assoc...
Article
4435 Von Willebrand Factor (VWF) is the cruical molecule in the initiation of hemostatic response to vascular injury. Quantitative or qualitative defects in VWF are associated with Type 1/Type 3 or Type 2 von Willebrand disease (VWD), respectively. VWF is encoded by the VWF gene composed of 52 exons and located on chromosome 12. Nonfunctional copy...
Article
Full-text available
Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.3 deletions and IGE. We then set out to determine the relative occurrence of sp...
Article
Factor VIII (FVIII) replacement therapy is ineffective in hemophilia A patients who develop alloantibodies (inhibitors) against FVIII. The type of factor 8 (F8) gene mutation, genes in the major histocompatibility complex loci, and also polymorphisms in IL-10 and tumor necrosis factor-alpha are the major predisposing factors for inhibitor formation...
Article
Full-text available
Benign familial neonatal convulsions (BFNC) is a rare monogenic subtype of idiopathic epilepsy exhibiting autosomal dominant mode of inheritance. The disease is caused by mutations in the two homologous genes KCNQ2 and KCNQ3 that encode the subunits of the voltage-gated potassium channel. Most KCNQ2 mutations are found in the pore region and the cy...
Article
Summary In order to determine the gene frequencies of nine polymorphic sites associated with FVIII and FIX genes in the Turkish population a sample of 50-235 unrelated X chromosomes from healthy individuals were analysed by using PCR-based assays. The Turkish population was found to be as polymorphic as Europeans in the FVII and FIX genes. Analysis...
Article
The most common cause for severe cases of hemophilia A is the homologous recombination involving intron 22 and related sequences outside the F8 gene. F8 coding regions of the gene including the exon/intron junctions were sequenced in 10 Turkish hemophilia A patients all of whom have been typed negative for intron 22 inversion and who did not have a...
Article
Hemophilia A is an X-linked bleeding disorder resulting mostly from heterogeneous point mutations in the factor VIII (F8) gene. Small/large gene deletions, insertions and gross gene rearrangements underlie the molecular pathogenesis of the disease. Two large inversion mutations due to intrachromosomal recombinations between inverted repeats found i...
Article
Heterogeneous mutations in the coagulation factor IX (FIX) gene result in a bleeding tendency known as haemophilia B. The haemophilia B mutation database has a total of 2353 patient entries, including 10 of the estimated 1000 Turkish patients. In this study, a more comprehensive analysis of the molecular pathology of haemophilia B in Turkey reveale...