Browsing by Author "Alehan, Fusun"

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22q13.3 Deletion Syndrome: An Underdiagnosed Cause of Mental Retardation
(2015) Erol, Ilknur; Onay, Ozge Surmeli; Yilmaz, Zerrin; Ozer, Ozge; Alehan, Fusun; Sahin, Feride Iffet
Phelan-McDermid syndrome, also known as 22q13.3 deletion syndrome, is characterized by global developmental delay, absent or delayed speech, generalized hypotonia, and minor physical anomalies. The deletion typically involves the terminal band 22q13.3 and has been associated with both familial and de-novo translocations. We report the case of an 11-year-old Turkish girl with 22q13.3 deletion syndrome presenting with repeated seizures during the course of a rubella infection. We also review the clinical features of 22q13.3 deletion syndrome and emphasize the importance of considering a rare microdeletion syndrome for idiopathic mental retardation when results of a routine karyotype analysis are normal. To the best of our knowledge, this is the first reported case of a Turkish patient with isolated 22q13.3 deletion syndrome.
ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients
(2016) Alehan, Fusun; 26931382
Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over 100 genes leading to impaired protein or lipid glycosylation. ALG1 encodes a beta 1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date 13 mutations in 18 patients from 14 families have been described with varying degrees of clinical severity. We identified and characterized 39 previously unreported cases of ALG1-CDG from 32 families and add 26 new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2, was seen in all 27 patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder. (C) 2016 Wiley Periodicals, Inc.
Cerebellar Mutism Caused by Primary Varicella Infection in an Immunocompetent Child
(2014) Erol, Ilknur; Ozkale, Yasemin; Saygi, Semra; Alehan, Fusun; https://orcid.org/0000-0002-3530-0463; https://orcid.org/0000-0002-8522-5078; 23446802; AAK-4825-2021; AAB-1203-2021
Varicella (chickenpox) is a common childhood infection caused by the varicella-zoster virus, which is often self-limiting and usually benign. Although uncommon, neurologic complications of varicella have been documented that include postinfectious cerebellar ataxia, meningoencephalitis, Reye syndrome, myelitis, optic neuritis, stroke, Guillain-Barre syndrome, seventh cranial nerve palsy, and Ramsay-Hunt syndrome. In this case study, the authors describe a 7-year-old girl who presented with varicella skin rash with unsteady gait and anarthria on day 2, and her condition was attributed to cerebellar mutism. To date, this complication has never been reported in a child with primary varicella infection. Therefore, this case study documents a rare but serious complication of childhood chickenpox.
Early clinical predictors of intractable epilepsy in childhood
(2014) Saygi, Semra; Erol, Ilknur; Alehan, Fusun
Aim: In this retrospective study, we evaluated the clinical responses to antiepileptic drug (AED) therapy in pediatric epilepsy patients treated at a single center. Materials and methods: We identified 28 children with intractable epilepsy and 213 patients with drug-responsive epilepsy. Results: Univariate analysis showed that age at onset, high (daily) initial seizure frequency, infantile spasm, history of neonatal seizures, abnormal neurodevelopmental status, neurological abnormalities, mental retardation, remote symptomatic etiology, and abnormal brain imaging results were significant risk factors for the development of intractable epilepsy (P < 0.05). Multivariate logistic regression analysis revealed that high (daily) initial seizure frequency and remote symptomatic etiology were significant and independent risk factors for intractable epilepsy (P < 0.05). Conclusion: Our study suggests that the risk of developing intractable epilepsy in childhood may be predicted, to some extent, by the early clinical course. Early identification of patients at high risk of developing intractable epilepsy will guide appropriate therapy and reduce exposure to ineffectual treatments.
Hyperventilation During Routine Electroencephalography: Are Three Minutes Really Necessary?
(2015) Watemberg, Nathan; Farkash, Michael; Har-Gil, Miki; Sezer, Toner; Goldberg-Stern, Hadassah; Alehan, Fusun; 0000-0002-2278-1827; 25661285; AAJ-5931-2021
OBJECTIVE: Hyperventilation induces absence seizures in children with absence epilepsy, and routine electroencephalography studies include three minutes of hyperventilation. We studied the duration of hyperventilation required to provoke a first absence seizure to determine whether three minutes of the procedure are indeed necessary. METHODS: Electroencephalography records of children who experienced absence seizures during hyperventilation were reviewed. The time from hyperventilation onset to a first and further seizure(s) was measured, and the occurrence of absences during the posthyperventilation phase was also noted. RESULTS: Sixty-two studies were evaluated. Mean time from hyperventilation onset to a first absence was 52 seconds (median 32 seconds). The vast majority (85.5%) had an absence within 90 seconds. Most (68%) children sustained a single event. All eight children with posthyperventilation seizures had experienced at least one event during hyperventilation. CONCLUSIONS: Our findings suggest that current guidelines for routine pediatric electroencephalography recording requiring three minutes of hyperventilation may not be clinically necessary. We found that the vast majority of children referred for suspected absence seizures experience a seizure less than 90 seconds after hyperventilation onset, and even more so by 120 seconds. Hence, a larger prospective study is warranted to establish more accurate hyperventilation duration parameters. We also suggest that once an absence seizure has been recorded at any time during hyperventilation, this procedure could be stopped, thus reducing the amount of discomfort for the child.
Is Celiac Disease an Etiological Factor in Children with Nonsyndromic Intellectual Disability?
(2016) Sezer, Taner; Balci, Oya; Ozcay, Figen; Bayraktar, Nilufer; Alehan, Fusun; https://orcid.org/0000-0002-2278-1827; https://orcid.org/0000-0002-8402-8208; https://orcid.org/0000-0002-5214-516X; https://orcid.org/0000-0002-7886-3688; 26078418; AAJ-5931-2021; AAI-9346-2021; ABG-5684-2020; Y-8758-2018
To determine the prevalence of celiac disease in children and adolescents with nonsyndromic intellectual disability, we investigated serum levels of tissue transglutaminase antibody and total IgA from 232 children with nonsyndromic intellectual disability and in a healthy control group of 239 children. Study participants who were positive for tissue transglutaminase antibody underwent a duodenal biopsy. A total of 3 patients in the nonsyndromic intellectual disability group (5.45%) and 1 in the control group (0.41%) had positive serum tissue transglutaminase antibody (P > .05). Duodenal biopsy confirmed celiac disease in only 1 patient who had nonsyndromic intellectual disability. In this present study, children with nonsyndromic intellectual disability did not exhibit a higher celiac disease prevalence rate compared with healthy controls. Therefore, we suggest that screening test for celiac disease should not be necessary as a part of the management of mild and moderate nonsyndromic intellectual disability. However, cases of severe nonsyndromic intellectual disability could be examined for celiac disease.
Multidrug Resistance 1 (MDR1) 3435C/T Genotyping in Childhood Drug-Resistant Epilepsy
(2014) Saygi, Semra; Alehan, Fusun; Atac, Fatma Belgin; Erol, Ilknur; Verdi, Hasibe; Erdem, Remzi; https://orcid.org/0000-0002-8522-5078; https://orcid.org/0000-0001-6868-2165; https://orcid.org/0000-0002-3530-0463; https://orcid.org/0000-0003-0591-009X; https://orcid.org/0000-0002-7537-2170; 23465586; AAB-1203-2021; ABG-9966-2020; AAK-4825-2021; ABG-9940-2020
Introduction: A mutation at nucleotide position 3435 in exon 26 of the multidrug resistance 1 (MDR1) gene is the most frequently studied polymorphism in relation to multidrug resistance. However, there are conflicting data as to whether the CC or TT genotype of the 3435C>T polymorphism is associated with drug resistance. Methods and results: We investigated the association between this polymorphism in drug-resistant childhood epilepsy by comparison with drug-responsive patients. In total, 59 patients with drug-resistant epilepsy, defined as having four or more seizures within a 12-month period while using three or more AEDs, 60 children with drug-responsive epilepsy who had remained seizure-free for 12 months on their current AED regimen and 76 healthy children were involved in this study. Genotype frequencies in drug-resistant patients were as follows: 32.2% CC, 44.1% CT, 23.7% TT; in the drug-responsive group: 20.0% CC, 50.0% CT, 30.0% TT; in the control group: 24.3% CC, 50.0% CT, 25.7% TT. Comparison of drug-resistant and drug-responsive patients revealed no significant difference in genotype frequency. The findings of the epilepsy patients were not significantly different from those of the healthy control subjects. Conclusions: Our study does not support any significant association between the MDR1 polymorphism and drug-resistant childhood epilepsy. (C) 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Novel Deoxyguanosine Kinase Gene Mutations in the Hepatocerebral Form of Mitochondrial DNA Depletion Syndrome
(2015) Sezer, Taner; Ozcay, Figen; Balci, Oya; Alehan, Fusun; 0000-0002-5214-516X; 0000-0002-2278-1827; 0000-0002-8402-8208; 24423689; ABG-5684-2020; AAJ-5931-2021; AAI-9346-2021
Deoxyguanosine kinase (DGUOK) gene mutations have been identified in the hepatocerebral form of mitochondrial DNA depletion syndromes. We report here clinical and laboratory features of 3 infants with novel DGUOK gene mutations, c.130G>A (Glu44Lys), c.493G>A (Glu165Lys), and c.707+3_6delTAAG.
Superoxide Dismutase and Catalase Genotypes in Pediatric Migraine Patients
(2015) Saygi, Semra; Erol, Ilknur; Alehan, Fusun; Yalcin, Yaprak Yilmaz; Kubat, Gozde; Atac, Atac, Fatma Belgin; 0000-0002-3530-0463; 0000-0001-6868-2165; 0000-0002-9337-9106; 0000-0002-8522-5078; 25818327; AAK-4825-2021; ABG-9966-2020; ABB-4078-2020; AAB-1203-2021
This study compared superoxide dismutase (SOD) and catalase (CAT) alleles in 97 consecutive children and adolescents with migraine to 96 healthy children and adolescents. Isolated genomic DNA was used as a template for SOD1 (35 A/C), SOD2 16 C/T, and CAT2 [(-262 C/T) and (-21 A/T)] allele genotyping. The SOD2 16 C/T genotype and C allele frequency differed significantly between controls and migraine (P = .047; P = .038). CAT -21 AA genotype and A allele frequency were significantly higher in both migraine with aura patients (P = .013; P = .004) and migraine without aura patients (P = .003; P = .001) compared to controls. To our knowledge, this is the first demonstration of differences in SOD and CAT genotypes between pediatric migraine patients and age-matched controls. Further studies on the functional implications of these genetic variants on neural antioxidant capacity and the use of antioxidant modulators for migraine treatment are warranted.
TGF-β1 Genotype in Pediatric Migraine Patients
(2015) Saygi, Semra; Alehan, Fusun; Erol, Ilknur; Yalcin, Yaprak Yilmaz; Atac, Fatma Belgin; Kubat, Gozde; 0000-0002-3530-0463; 0000-0002-9337-9106; 0000-0002-8522-5078; 0000-0001-6868-2165; 24619148; AAK-4825-2021; ABB-4078-2020; AAB-1203-2021; ABG-9966-2020
There is no information about the role of transforming growth factor-beta 1 (TGF-1) in the pathogenesis of pediatric migraine. This study included 100 consecutive children and adolescents in whom migraine was diagnosed and 88 healthy children and adolescents. The isolated genomic DNA was used as a template for TGF-1 (-800G/A, -509C/T, 869T/C [codon 10] and 915G/C [codon 25]) genotyping. The allelic frequency of 509C/T was significantly different between control and migraine without aura patients (P = .04). Codon 10 C/T genotypic and C10 C allelic frequency of TGF-1 polymorphisms were significantly higher in migraine and migraine without aura patients versus healthy controls (P = .00; P = .00). To our knowledge, this is the first report dealing with the relationship between TGF-1 genotype and migraine in the pediatric age group. Further studies related to this subject are needed, along with a search for new therapeutic agents with anti-inflammatory properties.
West Syndrome Associated with A Novel Chromosomal Anomaly; Partial Trisomy 8P Together with Partial Monosomy 9P, Resulting from A Familial Unbalanced Reciprocal Translocation
(2015) Erol, Ilknur; Saygi, Semra; Demir, Senay; Alehan, Fusun; Sahin, Feride Iffet; 0000-0002-8522-5078; 0000-0001-7308-9673; 0000-0002-4209-9075; 0000-0002-3530-0463; 25878738; AAB-1203-2021; AAC-7232-2020; AAK-9310-2021; AAK-4825-2021
West syndrome is classified according to the underlying etiology into an acquired West syndrome, a congenital/ developmental West syndrome, and West syndrome of unknown etiology. Causes of a congenital/ developmental West syndrome are extensive and include chromosomal anomalies. We report on a patient carrying a derivative chromosome originating from the reciprocal unbalanced translocation t (8;9) (p11.2;p22) and presenting with macrocephaly, West syndrome, severe mental motor retardation and hypotonia. As far as we know, this is a new chromosomal anomaly associated with West syndrome.