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Dominant pathogenic mutations in the TRPV4 gene give rise to a wide spectrum of abnormal phenotypes, including bone dysplasia as well as spinal muscular atrophy and hereditary motor and sensory neuropathy. Spondyloepimetaphyseal dysplasias (SEMDs) are autosomal dominant skeletal dysplasias characterized by mild epiphyseal dysplasia, flared metaphyses, prominent joints, spondyler dysplasia, and brachydactyly with various carpal, metacarpal, and finger malformations.We present a boy who has the clinical and radiological signs of SEMD-M with a dominant TRPV4 mutation. He also has some striking findings that have not been seen in these patients before, and they may be able to provide assistance to medical professionals in the process of diagnosis.These include a shorter distance between his lumbar vertebrae, congenital contractures, and an arachnoid cyst.

Background: Alzheimer’s disease is a multifactorial, neurodegenerative disease which is considered the most common cause of dementia. It is divided into two subtypes based on the age of onset: Early-Onset Alzheimer’s Disease (EOAD) and Late-Onset Alzheimer’s Disease (LOAD). Objective: In this study, we aimed to analyse the polymorphisms of APOE2/E3/E4, ACE I/D, PICALM rs3851179, which are thought to increase the risk of disease, and CYP2D6 rs1080985, that affects the therapy response. Methods: 102 early onset and 99 late onset Alzheimer's patients diagnosed according to DSM-IV and NINCDS-ADRDA diagnostic criteria were included in the study. MMSE test was applied at the time of diagnosis and the control examination was performed after 6 months. We analysed the polymorphisms of APOE2/E3/E4 by fragment analysis and ACE I/D, PICALM rs3851179, CYP2D6 rs1080985 by Real Time- PCR. The response of the therapy and effects on prognosis were compared between groups by Mini-Mental State Exam test scores. Results: The score differences of the women were significantly lower than men’s score differences. The score differences of the EOAD group were significantly lower than the LOAD group in women. Family history situation was higher in men compared to women. The score differences were higher at CC genotype for PICALM rs3851179 in the EOAD group; the score differences were higher at E3/E4 genotype than E2/E2 genotype in LOAD. Also, the score differences were significantly higher at PICALM rs3851179 in the acetylcholinesterase inhibitor+antidepressant therapy group. Conclusions: The relationship between the treatment groups and related gene regions was investigated extensively for the first time in the literature. As a result, it will be a guide in the clinic in light of the findings of the prognosis and pharmacogenetic interactions of the disease obtained from the study.

Background and aim: The number of reports on the role of tubulin gene mutations (TUBA1A, TUBB2B, and TUBB3) in etiology of malformations of cortical development has peaked in recent years. We aimed to determine tubulin gene defects on a patient population with simple and complex malformations of cortical development, and investigate the relationship between tubulin gene mutations and disease phenotype.Materials and methods: We evaluated 47 patients with simple or complex malformations of cortical development, as determined by radiological examination, for demographic features, clinical findings and mutations on TUBA1A, TUBB2B, and TUBB3 genes. Results: According to the magnetic resonance imaging findings, 19 patients (40.5%) had simple malformations of cortical development and 28 (59.5%) patients had complex malformations of cortical development. Focal cortical dysplasia was the most common simple malformation, lissencephaly was the most common coexisting cortical malformation, and corpus callosum anomalies were the most common coexisting extracortical neurodevelopmental abnormalities. None of the patients had genetic alterations on TUBA1A, TUBB2B, and TUBB3 genes causing protein dysfunction. On the other hand, the frequencies of some polymorphisms were higher when compared to the literature.Conclusion: It is crucial to identify the etiology in patients with malformations of cortical development in order to provide appropriate genetic counseling and prenatal diagnosis. We consider that multicenter studies with higher patient numbers and also including other malformations of cortical development-related genes are required to determine underlying etiological factors of malformations of cortical development patients.

Background and Aims:PCDH19 gene, which encodes protocadherin 19, is associated with epilepsy and intellectual disability, mainly in affected females. The clinical manifestations are heterogeneous and the main features include early onset seizure, generalized or focal seizures sensitive to fever, and brief seizures occurring in clusters. The disorders exhibit a unique and unusual X-linked pattern of expression. We aimed to investigate PCDH19 mutations/deletions in patients with epilepsy and describe the clinical/molecular features. Methods: PCDH19 gene was analyzed in 35 Turkish female patients from 34 families with early-onset epilepsy via direct sequencing and multiplex ligation-dependent probe amplification analysis. Additionally, array comparative genomic hybridization analysis was performed in patients with whole gene deletion. Results: We identified 2 different heterozygous mutations in 2 unrelated probands (5. 7%) which were located in exon 1. Additionally, whole gene deletions were detected in dizygotic twin girls (5. 7%), who had distinct clinical features and the deletion was inherited from the unaffected father. The second twin suffered more severe clinical manifestations including autistic features, behavioral problems, mild-moderate mental retardation and seizures, which were under control with multidrug regimen when compared with the first twin. Conclusion: PCDH19 is a major causative gene in patients with epilepsy and further data is required to gain a better understanding of phenotype-genotype correlation. In addition to gene sequencing, deletion/duplication analysis will improve the molecular diagnosis in patients with clinical findings.

BACKGROUND Functional constipation is an important clinical problem among chidren all over the world. Its main cause is not completely understood. Motilin is a gastrointestinal hormone that increases intestinal motility. In this study, we aimed to investigate the serum motilin levels and its relationship with stool consistency and motilin gene polymorphisms in constipated children. METHODS In this study we investigated 91 constipated patients (mean age 6.84±3.55 years) and 100 healthy controls (mean age 7.78±4.25 years). Serum motilin levels were assessed by sandwich enzyme-linked immunosorbent assay. rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) mutations were evaluated for motilin gene polymorphisms. RESULTS Serum motilin levels were significantly lower in constipated children than healthy controls (6.20±7.86 vs. 11.54±17.89 pg/mL, respectively, P=0.008). Serum motilin levels were significantly correlated with Bristol stool scale rate (r=0.193, P=0.011) in whole study group, but in the constipation group there was no significant correlation (r=-0.072, P=0.528). There were no differences in terms of presence or distribution of the polymorphisms of rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) in both groups. There was not a significant difference between different polymorphism groups regarding serum motilin concentrations in whole study group and also in both of the study groups. CONCLUSIONS This study indicated for the first time that serum motilin levels decreased in constipated children. Further studies are needed to clarify whether motilin or motilin gene polymorphisms has a role in pathogenesis of functional constipation.

There are numerous causes, such as environmental factors, medications, endocrine disorders, and genetic factors, that can lead to obesity. However, severe early-onset obesity with abnormal feeding behavior, mental retardation, dysmorphic features, organ-specific developmental abnormalities, and endocrine disorders suggest a genetic etiology. Mutations in genes related to the leptin-melanocortin pathway play a key role in genetic obesity. This pathway controls hypothalamic regulation of food intake. A few cases have been reported to have mutations in leptin (LEP) or leptin receptor (LEPR) genes. The cases had severe early-onset obesity, hyperphagia, and additional features, such as altered immune function, hypogonadism, and hypothyroidism. We present a 3-year-old male patient with severe early-onset obesity whose genetic analysis revealed a homozygous, novel, and pathogenic variant (c.1603+2T>C) in LEPR.

This study presents a nonamplification-based nucleic acid assay for the detection of single-nucleotide polymorphism (SNP) associated with familial Mediterranean fever (FMF) besides polymerase chain reaction (PCR)-based methodologies. The major objective is to show the potential of the proposed assay for rapid screening of FMF in a Mediterranean region of 400 million population. The assay relies on binding difference of specially designed wild and mutant primers to the target genomic DNA, followed by determination of unbound primers by quick titration of a cationic polythiophene reporter. The fluorescent reporter exhibits signal transition from 525 to 580 nm in the presence of unbound primers, and it correlates the binding affinity of label-free primers to the homozygous wild and mutant genomes. As a proof of concept, 26 real samples are studied relying on the ON and OFF fluorescence signals of the cationic polythiophene reporter. The results are analyzed by principal component analysis (PCA), which provides clear separation of healthy and patient individuals. The further analysis by support vector machine (SVM) classification has revealed that our assay converges to 96% overall accuracy. These results support that the PCR-free nucleic acid assay has a significant potential for rapid and cost-effective screening of familial Mediterranean fever.

A 12-year-old girl with bilateral stage 2B Coats disease was screened meticulously for a possible underlying systemic disease as she was female and the disease was bilateral. Full systemic workout turned out to be unremarkable. However, an ABCA4 gene mutation was found in the genetic analysis. NDP and TINF2 gene mutations were not present. She was successfully treated with a bilateral, single intravitreal injection of dexamethasone implant and a single session of indirect laser photocoagulation with a relatively good anatomic and functional result. To the best of our knowledge, the present case is the only reported case of Coats disease with an ABCA4 gene mutation. (C) 2018 The Author(s) Published by S. Karger AG, Basel

Thanatophoric dysplasia is one of thenewborn’s dwarfism syndromes usually resulting in death during perinatal periodand manifesting as short extremities. It is characterized by macrocephaly,prominent forehead, narrow thorax, short extremities, flattened vertebralbodies, curved femurs. This is caused by mutations in the fibroblast growthfactor receptor 3 (FGFR3) gene andshows autosomal dominant inheritance model. In this report, we presented a casewith abnormal USG findings during perinatal period and detected to carry ap.R248C mutation in FGFR3 gene inamniosynthesis fluid., Tanatoforik displazi, genelde perinataldönemde ölümle sonuçlanan ve kısa ekstremiteler ile kendini gösterenyenidoğanın cücelik sendromlarından biridir. Makrosefali, belirgin alın, dartoraks, vertebralarda düzleşme, ekstremitelerde kısalık, femurda eğrilme ilekarakterizedir. Fibroblast büyüme faktörü reseptörü 3 (FGFR3) genindeki mutasyonlardan kaynaklanır ve otozomal dominantkalıtım modeli gösterir. Bu makalede, prenatal dönemde anormal USG bulgularıolan, amniyosentez materyalinden yapılan FGFR3gen analizi ile p.R248C mutasyonu saptanan bir olgu anlatılmıştır.

Peritoneal fibrosis (PF) is a pathological change that occurs mostly long-term peritoneal dialysis (PD) patients, as a result of triggering the inflammatory response. Plasminogen activator inhibitor-1 (PAI-1) is an important molecule featured in the development of fibrosis. It has been shown in literature that PAI-1 gene alterations are associated with fibrosis in many tissues and organs. However, PAI-1 gene alterations in long-term PD patients have not yet been investigated. In this study, PAI-1 4G/5G polymorphism was examined by reverse hybridization, and all coding exons of the PAI-1 gene were examined by sequence analysis to provide treatment modification in patients with predisposition before fibrosis develops. The patients were divided into two groups according to ultrafiltration failure test and duration of PD treatment: those with suspected PF or a high probability of developing PF (36%) and those with a low probability of developing PF (64%). There was no significant difference between the two groups in findings such as peritoneal equilibration test (PET), Kt/V, the content of the PD solution used, peritonitis, and PAI-1 4G/5G polymorphism (P > .05). A total of eight gene alterations (rs2227660, rs2227668, rs2854233, rs41281004, rs61553169, rs368413856, rs2227684) were detected by sequence analysis, one of which was exonic (rs6092). When the genotype distributions of these variants were examined, no significant difference was found between the two groups. PAI-1 gene changes were not detected in patients with the probability of developing PF. There is a need for further studies involving other molecules responsible for predisposing to PF with larger patient populations in patients undergoing long-term PD treatment.

Aim: We aimed to share our genetic test results for SMA since 2001, and compare the commonly used screening and diagnostic methods for SMA.

Amaç: Çocuklarda; Duchenne/Becker Musküler Distrofisi (DBMD) duygusal ve davranışsal problemlerle ve aile fonksiyonlarında ki bozulma ile ilişkilidir. Bu çalışma, aile işlevselliğini ve davranış sorunlarını, DBMD olan olgularda araştırmayı amaçlamaktadır.Yöntemler: Çalışma; Ocak 2019 ve Mart 2019 tarihleri arasında Dokuz Eylül Üniversitesi Tıbbi Genetik ve Çocuk ve Ergen Psikiyatrisi Polikliniği’ne başvuran 28 DBMD tanılı çocuk ve ergen ile 50 sağlıklı kontrol olgusunu içermektedir. Duygulanım Bozuklukları ve Şizofreni Görüşme Çizelgesi-Şimdi ve Yaşam Boyu Şekli-Türkçe (K-SADS-PL) ile araştırmacılar tarafından değerlendirilen katılımcılara; sosyodemografik ve klinik özellikler ile ilgili sorular içeren veri formu, Wechsler Çocuklar İçin Zeka Ölçeği (WISC-R) (sadece DBMD vakaları), Beck Depresyon Ölçeği (BDI), Durum ve Süreklilik Kaygı Envanteri (STAI), Ebeveyn Tutum Değerlendirme Ölçeği (PARI), Çocuk Davranış Kontrol Listesi (CBCL) ve Aile Değerlendirme Ölçeği uygulanmıştır.Bulgular: DBMD'li çocukların anneleri, Beck Depresyon Envanteri ve Durum-Sürekli Kaygı Envanteri ölçeklerinde, kontrol grubundakilere göre endişeli ve depresif durumlarla ilişkili daha yüksek ancak istatistiksel olarak anlamlı olmayan puanlar saptanmıştır (sırasıyla P=0.888, P=0.584 ve P=0.646). DBMD vakaları, Çocuk Davranışları Kontrol Listesinin çoğunda (aktiviteler, çekingen / depresif, somatik şikayetler, vb.) anlamlı olarak daha yüksek puanlar göstermiştir; bu, ailelerin işleyişini ve hastanın yaşam kalitesini etkileyen birçok problem alanına sahip oldukları anlamına gelmektedir (P, Aim: Duchenne/Becker muscular dystrophy (DBMD) in children is associated with emotional and behavioral problems and impairment at family functioning. The current study aimed to explicate family functioning and child behavioral problems with DBMD.Methods: The study involved 28 child and adolescents with DBMD attending Dokuz Eylul University Medical Genetics and Child and Adolescent Psychiatry Outpatient Clinic from January 2019 to March 2019 and comprised 50 healthy control subjects. The participants who were evaluated with Kiddie-Sads-Present and Lifetime (K-SADS-PL) by blinded professionals completed a data form containing questions regarding sociodemographic and clinical features, Wechsler Intelligence Scale for Children-Revised (WISC-R) (for only DBMD cases), the Beck Depression Scale (BDS), State-Trait Anxiety Inventory (STAI), Parenteral Attitude Research Instrument (PARI), the Child Behavior Checklist (CBCL) and Family Assessment Device. Results: Mothers of the children with DBMD demonstrated higher scores in Beck Depression Inventory and State-Trait Anxiety Inventory scales, which is associated with anxious and depressive states as compared with those from the control group but not statistically significant (P=0.888, P=0.584 and P=0.646, respectively). DBMD cases demonstrated significantly higher scores in most of the Child Behavior Checklist (activities, withdrawn/depressed, somatic complaints etc.), meaning that they have many problem areas affecting family functioning and the quality of life of the patient (P

Introduction: In this study, we aimed to characterize the effect of methylation on clinical diversity and gene expression levels in familial Mediterranean fever. Materials and Methods: Forty children, who were diagnosed with FMF according to the Tel-Hashomer criteria, were included in the study. The control group consisted of 32 healthy children. Demographic data, results of molecular studies, physical examination findings, number of attacks, response to treatment were recorded. To test the possibility that methylation is responsible for different phenotypic reflections of mutations, we classified FMF patients with respect to MEFV mutations and studied the differences of MEFV mRNA, pyrin and methylation levels between different subgroups. Results: MEFV mRNA expression levels were significantly lower in FMF patients, compared to control subjects (P = 0.049). Consistent with this observation, pyrin levels were significantly lower in FMF patients (P = 0.037). In addition, we found that MEFV methylation level was higher in FMF patients compared to control subjects (P = 0.376). Conclusions: There was no evidence that differences in methylation levels could be responsible for variable effects of different mutations and variable clinics in the MEFV gene. Further studies on larger patient groups are necessary to identify the effects of different factors.

Objectives: We have no series report concerning genetic etiology of Alport Syndrome AS in our country. So, we aimed to investigate AS related pathogenic variants of COL4A3, COL4A4 and COL4A5 genes in index cases and their families who referred to our center.Patients and Methods: The study includes 32 subjects 17 index cases and their relatives who are investigated between years 2018-2019 by NGS targeting the coding regions of related genes. The test results and clinical findings of the cases are studied retrospectively.Results: By the presented study, 19 individuals identified to have COL4A3 and COL4A5 variations which could be important for the clinical management. In four cases, there are novel variants. In two cases, there are digenic variations. There is no clinically relevant variant in COL4A4 gene. The most frequent three mutations of COL4A5 gene reported in United States US are not determined in our study group.Conclusion: The diagnostic genetic tests of AS should be designed to include whole coding regions of COL4A3 and COL4A5 genes, not just for the frequently reported pathogenic variants. The cases without pathogenic variants by sequencing should be investigated for deletions/duplications of COL4A5 gene. Clinical findings of our cases with novel genetic variants are presented as a contribution to literature

Objectives: This study aims to investigate the clinical impact of the R202Q (c.605G>A) alteration of Mediterranean fever (MEFV) gene in children with familial Mediterranean fever (FMF). Patients and methods: Medical records of 115 patients (51 males, 64 females; mean age 6.6±3.8 years; range 8 months to 15.8 years) presenting with FMF pre-diagnosis were examined. Patients were classified into two groups based on number of mutated alleles (one-mutant allele and twomutant alleles), and these groups were classified into three subgroups (Group 1; subgroup 1: M694V/R202Q, subgroup 2: M694V/other, subgroup 3: other/other, and Group 2; subgroup 4: R202Q/-, subgroup 5: other/-, subgroup 6: -/-). Sex, age, abdominal pain, fever, arthritis or arthralgia, myalgia, erysipelas-like erythema, chest pain, amyloidosis, family history of FMF, and definitive FMF frequency were compared between groups. Results: The most common allele alterations were the heterozygous R202Q alteration (27%) and the compound heterozygous mutation M694V/ R202Q (20.9%). The R202Q alteration of MEFV gene was detected in 76 patients (66%) (15 homozygous). There was non-M694V (E148Q, V726A) mutation in two of these patients. One (50%) of the patients with isolated R202Q homozygous alteration and six (19%) of the patients with isolated R202Q heterozygous alteration had definitive FMF. In the two-mutant allele group; abdominal pain, fever, arthritis/arthralgia, and definitive FMF frequency were lower in subgroup 1 than subgroup 2. There was no significant difference in clinical findings and definitive FMF frequency between subgroup 2 and subgroup 3. In the one-mutant allele group, clinical findings did not differ between subgroups. Conclusion: R202Q alteration of the MEFV gene may lead to symptoms consistent with FMF. However, R202Q/M694V compound heterozygosity is more associated with mild phenotype than compound heterozygous mutation of M694V.

Background/aim: CHARGE syndrome is a rare autosomal dominant disease with multiple congenital anomalies and cognitive impairment, which is caused by mutations in the CHD7 gene. This study aimed to disclose the mild end of the phenotypic spectrum of CHARGE syndrome, which has a highly variable expressivity. Materials and methods: Twenty-one patients who had at least one of the major symptoms of CHARGE syndrome (coloboma, choanal atresia, characteristic ear anomalies, semicircular canal hypoplasia, and cranial nerve anomalies) were included in the study. All patients were tested for karyotype analysis and CHD7 gene mutation/deletion. Results: In the study population, 6 different mutations were detected in 5 patients, and 2 different polymorphisms were detected in the CHD7 gene in 3 patients. MLPA analysis of all coding exons of the CHD7 gene revealed no pathogenic deletion/duplication. Conclusion: CHARGE syndrome should be considered as a differential diagnosis to detect the mild end of the spectrum, even if the patient does not fit the criteria.

Horseshoe kidney is the most frequent renal fusion anomaly that is usually asymptomatic and isolated malformation. However it can be seen with various syndromes and chromosomal anomalies. It was reported that 15-35% of Turner syndrome cases (TS) also display horseshoe kidney condition. TS is a chromosomal anomaly that had been characterized by delayed puberty, short body height and gonadal dysgenesis. In this report a five-year-old girl with horseshoe kidney, which has growth retardation during follow-up as only symptom of Turner syndrome.

The CHARGE (coloboma, heart defects, atresia, retardation, genital, ear) syndrome is a genetic disease characterized by ocular coloboma, choanal atresia or stenosis and semicircular canal abnormalities. Most of the patients clinically diagnosed with CHARGE syndrome have mutations in chromodomain helicase DNA-binding protein 7 (CHD7) gene. The CHD7 gene is located on chromosome 8q12.1, and up to now, there are more than 500 pathogenic mutations identified in the literature. We report two patients diagnosed with CHARGE syndrome with two novel mutations in the CHD7 gene: the first patient has double consecutive novel mutations in three adjacent codons, and the other has a novel insertion.

Aim: To elucidate the genetic factors causing hyperbilirubinaemia in prolonged jaundice of the newborns, we investigated whether the HO-1 gene promoter polymorphism is a cause in unexplained pathological or prolonged jaundice. Methods: Three groups were defined: healthy newborns with no clinical jaundice, newborns hospitalized for jaundice without any identifiable pathological cause and newborns with prolonged jaundice associated with breast milk. Genomic DNA was extracted from the white blood cells and the promoter region of the HO-1 gene was amplified using PCR and their allelic repeats were determined. Results: We did not detect any significant difference in the allele frequencies between the healthy newborns and the newborns whose serum total bilirubin levels were >12.9 mg/dL. However, the patients with short (

Objectives This study aims to determine the carrier frequency and the most common mutations of the Mediterranean FeVer (MEFV) gene in healthy Cypriot population of Turkish origin. Patients and methods A total of 296 healthy participants (102 males, 194 females; median age 30 years; range 1 to 81 years) were evaluated. The exon 2, 3, 5 and 10 of MEFV genes were amplified by polymerase chain reaction. Results The participants demonstrated an extremely high carrier rate (12.5%). Most commonly detected mutations were E148Q and A74S, with rates of 7.3% and 2.8%, respectively. Conclusion Mediterranean FeVer gene mutation types and carrier rates in Turkish Cypriot population are different than other Mediterranean populations in the region. MEFV mutation carriage is frequent in North Cyprus and familial Mediterranean fever might be one of the causes for end stage renal disease in Turkish Cypriots.

To elucidate the genetic factors causing clinical differences in the children with Down syndrome and evaluate possible maternal risk factors, the researchers have investigated GSTM1, GSTT1, GSTP1 gene polymorphisms. Four groups were defined: group I (n = 52), children with Down syndrome; group II (n = 70), healthy children; group III (n = 52), mothers of the children with Down syndrome; and group IV (n = 69), mothers of the healthy children. Genomic DNA was extracted from the white blood cells and GenID (R) GmbH kit used for GST MI, T1 and PI gene amplification to determine polymorphisms. The researchers did not detect any significant difference in the allele frequencies between groups I and II, nor groups III and IV. The data indicated no relationship between detected GST polymorphisms, neither with Down syndrome nor with the risk of having an infant with Down syndrome.

Background/aims: Irritable bowel syndrome is a multifactorial functional gastrointestinal disorder affecting more than 10% of world population. Genetic component in pathophysiology of irritable bowel syndrome is still unknown. The aim of this study was to examine the potential impact of C-1291G polymorphism in alpha 2-adrenergic receptor gene promoter region in the etiology of the disease. Materials and Method: This prospective case-control study included 100 irritable bowel syndrome patients and 100 healthy controls adjusted for sex and age. The subjects were genotyped by using polymerase chain reaction amplification of the promoter region of alpha 2-adrenergic receptor gene. Allele and genotype frequencies were compared in patient and control groups. The study was approved by the University ethics committee. Results: The frequency of C allele was 72% and 75%, G allele was 28% and 25% in patient and control groups, respectively (p>0.05). We found that the frequencies of C1291C, C1291G, and G1291G genotypes were 50, 44, and 6%, respectively, in the patient group and 51, 48, and 1%, respectively, in the control group (p>0.05). The subgroup analysis of patients revealed that 70 patients were constipation-predominant, 27 patients were alternating diarrhea and constipation, and 3 patients were diarrhea-predominant irritable bowel syndrome. Conclusion: No significant association was observed between alpha 2-adrenergic receptor gene C-1291G polymorphism and irritable bowel syndrome in Turkish population. The high number of constipation predominant irritable bowel syndrome and very low number of diarrhea predominant irritable bowel syndrome patients might be the reason for statistical non-significance since alpha 2-adrenergic receptor gene is found to be responsible for mediating intestinal antisecretory action and probably is involved in the pathogenesis of diarrhea predominant irritable bowel syndrome. Further investigations are needed.

Polymorphisms of plasminogen activator inhibitor-1 (PAI-1) and angiotensin-converting enzyme (ACE) genes have been implicated in susceptibility to asthma. In this study, we aimed to investigate whether there was any association between childhood asthma and polymorphisms of the PAI-1 and ACE genes.Two hundred and three Turkish children aged 5-15 years, including 102 asthmatic patients and 101 healthy control subjects were included in this study. The asthma group was divided into two groups as follows: Group I: Asthmatic children with positive family history for atopy (n=53), Group II: Asthmatic children without any family history for atopy (n=49). One hundred and twenty-eight atopic family members were also included in the study. The insertion/deletion (I/D) polymorphism of the ACE and PAI-1 4G/5G gene polymorphisms was carried out by polymerase chain reaction.The prevalence of the PAI-1 4G allele was significantly greater in asthmatic children compared to control group (p0.05, OR: 1.64 (1.11-2.43)) but there was no significant relation between ACE I/D genotypes and childhood asthma. No significant difference was detected between Groups I and II in terms of these ACE and PAI-1 genotypes and allele frequencies. No significant relationship was found between both gene polymorphisms and total serum IgE and skin prick test results.It has been established that PAI-1 4G allele may be a genetic risk factor for childhood asthma but ACE gene I/D polymorphisms do not play a role in the development of asthma in the sample of Turkish children.

A disintegrin and metalloprotease domain 33 (ADAM33) is the first asthma-susceptible gene discovered by positional cloning. The objective of this study was to determine the association between ADAM33 polymorphisms and asthma in the Turkish children population with asthma. Four single-nucleotide polymorphisms (SNPs) previously reported to be related with asthma were genotyped in 98 cases and 100 controls. The genotyping procedure consisted of a polymerase chain reaction amplification and SNP detection of the 12433 T/C (T1), 12462 C/T (T2), 12540 C/T (T+1), and 12601 T/G (T+2) variants of the ADAM33 gene. No significant differences were observed for T1, T2, T+1, and T+2 polymorphisms between asthmatic patients and controls. There was also no difference between the atopic and nonatopic asthma group by means of ADAM33 polymorphisms. Our data revealed that there is no association of these 4 SNPs of the ADAM33 gene with asthma in the Turkish children population.

Brain-derived factor (BDNF) is a member of neurotrophin family and is localized and upregulated in areas implicated in epileptogenesis. Several lines of evidence make the BDNF gene a plausible candidate gene for predisposition to epilepsy. In this study, we tested that BDNF might be involved in the etiology of childhood PE. To assess whether BDNF gene C270T polimorphism could be implicated in vulnerability to PE, we conducted a case-control association analysis (112 partial epileptic and 100 controls) in Turkish children. Epileptic children were divided into two groups: 1—idiopathic (n=85) and 2—symptomathic epilepsy (n=27). There was no significant difference in genotypic distribution and allelic frequencies of the BDNF gene C270T polimorphism between the PE and control groups. However, the BDNF gene TT genotype was more frequently seen in the epileptic children (15 versus 11 patients, resp.). Interestingly, in the epilepsy group, both two children with TT genotype have posttraumatic epilepsy. The data indicate a possible association with the 270T genotype of the BDNF gene with a posttraumatic epilepsy. To draw any conclusion, further studies using larger sample sizes should be carried out in various ethnic populations in childhood epilepsies.

Amaç: Apolipoprotein E gen polimorfizmi ile lipid metabolizması arasındaki ilişki populasyon çalışmalarında ortaya konulmuştur. Obez olan çocuklarda apolipoprotein E gen polimorfizmi ile plazma lipid düzeyleri arasındaki ilişki ve obezite ile birlikte olan dislipidemilerde apolipoprotein E gen polimorfizmi araştırılmıştır. Yöntemler: İnsülin bağımlı diyabeti, karaciğer ve böbrek yetmezliği bulunmayan, plazma lipid düzeyini etkileyecek ilaç kullanmayan, primer obezitesi bulunan 57 çocuk ve normal kilolu 18 çocuk olmak üzere toplam 75 çocuğun plazma lipid düzeylerine bakılmış ve apolipoprotein E (Apo E) gen polimorfizmi polimeraz zincir reaksiyonu ile analiz edilmiştir. Bulgular: Obez çocuklarda Apo AI düzeyleri yüksek saptanmıştır. Obez ve obez olmayan grupta E2/E3 dağılımı sırasıyla %10,5, %27,8; E3/E3 dağılımı sırasıyla %80,7, %61; E3/E4 dağılımı sırasıyla %7, %5,6 olarak bulunmuştur. Obez olan grupta E4/E4 fenotipi, obez olmayan grupta E2/E4 fenotipi görülmemiştir. Obez olan grupta E2/E4 dağılımı %1,8, obez olmayan grupta E4/E4 fenotip dağılımı %5,6 bulunmuştur. Allel sıklıkları obez ve obez olmayan grupta sırasıyla epsilon 2 (?2) alleli için %6,1, %14; epsilon3 (?3) alleli için %89,5, %78; epsilon 4 (?4) alleli için %4,4, %8 olarak benzer bulunmuştur. Bütün gruplarda en sık allelin ?3 olduğu görülmüştür. Sonuç: Apo E allel ve fenotip dağılımının obez ve sağlıklı çocuklarda benzer olduğu gözlenmiştir. Obez çocuklarda total kolesterol, Apo B, Apo AI ortalama düzeyi, obez olmayan çocuklara göre daha yüksek bulunmuş, trigliserid düzeyleri obez olan grupta obez olmayan gruba göre belirgin yükseklik göstermiştir., Objective: The relationship between Apolipoprotein E (Apo E) gene polymorphism and lipid metabolism was presented by the population studies. The aim of this study was to search the relationship between Apo E gene polymorphism and plasma lipid levels in obese children and to search Apo E gene polymorphism in dislipidemias coexisting with obesity.Methods: Seventy five children (57 were primary obese, 18 were normal weight) were analysed by polymerase chain reaction for Apo E gene polymorphism and plasma triglyceride, HDL, LDL and Apo B amounts were evaluated. Excluding criterias for the study group are insulin dependent diabetes mellitus, hepatic and renal failure and medication because of they might affect the lipid concentration in plasma. Results: The Apo AI levels were significantly elevated in obese children. HDL, LDL and Apo B levels were nearly at the same levels while triglycerides levels were much higher in obese group than non-obese group, but the difference was not found statistically significant. In obese and non-obese group the E2/E3 distribution was 10.5% and 27.8%; E3/E3 was 80.7% and 61% and E3/E4 was 7% and 5.6% respectively. The E4/E4 phenotype was not determined in obese group while the E2/E4 phenotype was not seen in non-obese group. E2/E4 distribution was 1.8% in obese children and E4/E4 distribution was 5,6% in non-obese children . Allele frequencies in obese and non-obese children for epsilon 2 (ε2) were found as 6.1% and 14%; for epsilon 3 (ε3) 89.5% and 78% and for epsilon 4 (ε4) 48% and 4% respectively. There was no significant difference between the groups according to allele frequency (p>0.05). The ε3 was found the most frequent allele in all the groups. Conclusion: Apo E allele and phenotype distribution were found similar in obese and non-obese children. The Apo AI levels were significantly elevated in obese children.

Amyloidosis is the major complication of familial Mediterranean fever (FMF). Toll-like receptors (TLR) are involved in the activation of an innate immune system TLR-2 and TLR-4 recognize lipoteichoic acid and lipopolysaccharides (LPS), respectively. While TLR-2 Arg753Gln polymorphism upregulates, TLR-4 Asp299Gly and Thre399Ile polymorphisms downregulate inflammation. We investigated the effect of these polymorphisms on the development of amyloidosis in FMF patients. We also investigated myeloid cell TLR-2 and TLR-4 expressions in these patients. We studied 26 FMF patients and 13 FMF patients with amyloidosis. TLR-2 Arg753Gln and TLR-4 Asp299Gly and Thr399Ile polymorphisms were analyzed with the polymerase chain reaction-restriction fragment length polymorphism method. Myeloid cell baseline TLR-2 and TLR-4 and LPS-induced TLR-4 expressions were evaluated. The TLR-2 and TLR-4 polymorphism rate was compared with the results of 100 healthy subjects in our previous study. In addition, 13 healthy controls were enrolled for leukocyte TLR-2 and TLR-4 expressions. Serum amyloid A (SAA) levels were measured in these 13 control cases and in FMF patients during attack-free periods. The frequency of TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms in healthy controls in our previous study were 1%, 3%, and 2%, respectively. The frequency of these polymorphisms were not different in FMF patients (with or without amyloidosis) compared to the control group. Likewise, myeloid cell TLR-2 and TLR-4 expressions were not different among the controls and FMF patients. However, LPS-induced TLR-4 expression in granulocytes was more prominent in FMF patients. There was no correlation between TLR-2 and TLR-4 expressions and SAA levels. Neither myeloid cell TLR-2 and TLR-4 expressions nor TLR-2 Arg753Gln, TLR-4 Asp299Gly, and Thr399Ile polymorphisms seem to affect the development of secondary amyloidosis in FMF patients in our study population.

OBJECTIVE: The role of coagulation parameters left atrial thrombus formation in atrial fibrillation has not been investigated before. We aimed to investigate the association between the beta-fibrinogen gene polymorphism or glycoprotein IIIa gene polymorphism and presence of left atrial (LA) thrombus or spontaneous echo contrast (SEC) in patients with atrial fibrillation (AF). METHODS: Forty-seven patients with AF, in whom transesophageal echocardiography was performed, were included to this cross-sectional observational study. Patients were divided in two groups; those with LA thrombus (n=24) were assigned to group 1 and those without thrombus in group 2 (n=23). DNA analysis was conducted to determine gene polymorphism in all patients. Mann-Whitney U test or Chi-square tests were used for statistical analysis. RESULTS: There were no significant differences between groups regarding to demographic and clinical characteristics. The frequency of beta-fibrinogen 455 G/A polymorphism was higher (37.5%) in group 1 as compared to group 2 (15.1%) but it did not reach statistical difference (p=0.23). When we added patients with severe SEC in the study group (patients with severe SEC and/or thrombus n=27) the difference (44.40%-10%) reached the statistical difference (p=0.01). Glycoprotein IIIa Pl A1/A2 polymorphism was not different between groups with (p=0.82) or without SEC (p=0.73). CONCLUSION: In patients with atrial fibrillation, beta-fibrinogen 455 G/A gene polymorphism is associated with the presence of left atrial thrombus and severe SEC. Beta-fibrinogen 455 G/A gene polymorphism may be a promising marker for the prediction of thromboembolism risk in patients with atrial fibrillation.

An 8-month-old girl and a 20-month-old boy who presented with motor and developmental delay and long-standing fever are presented. The patients were diagnosed as Angelman syndrome with fluorescence in situ hybridization (FISH) analysis. Despite extensive clinical and laboratory examinations, no inflammatory or infectious origin for the fever was found. It was considered that the long-standing fever observed in these cases was due to hypothalamic dysfunction for thermoregulation.

Apolipoprotein E is consistently associated with the progression of some common human neurodegenerative diseases, e.g., epilepsy. We hypothesized that genetic variations in the apolipoprotein E gene have implications for susceptibility to, and prognoses in, febrile convulsion, which plays an apparent role in the development of epilepsy. We used the polymerase chain reaction and restriction enzyme digestion to characterize variations of the apolipoprotein E gene. Sixty-nine patients with febrile convulsion (simple/complex) and a corresponding cohort of healthy patients (n = 75) were used. There was no significant difference in genotypic distribution and allelic frequencies of the apolipoprotein E gene between the febrile convulsion and control groups. Comparing subpopulations of the febrile convulsion group (patients with simple and complex febrile convulsion), we noted that no patients with the epsilon 3/epsilon 4 genotype had complex febrile convulsions. The apolipoprotein E epsilon 3/epsilon 4 genotype was more frequently seen in the simple febrile than in the complicated febrile convulsion group (9 versus 0 patients, respectively). The data indicate an association with the epsilon 3/epsilon 4 genotype of the apolipoprotein E gene with a milder phenotype. Although apolipoprotein E4 is not a vulnerability factor regarding febrile convulsions, it seems effective in regard to prognoses. (C) 2008 Published by Elsevier Inc.

In this study, we investigated whether a TATA box polymorphism in the promoter of the UGT1*1 exon I, the most common detected DNA polymorphism in Gilbert’s syndrome, is a contributory factor in unexplained pathologic or prolonged jaundice. 38 neonates who had unexplained pathologic jaundice, 37 neonates who had unexplained prolonged jaundice, and 35 healthy, nonjaundiced neonates were enrolled in the study. Genotypes were assigned as follows: 6/6 (homozygous for a normal allele bearing the sequence [TA]6TAA), 7/7 (homozygous for an abnormal allele with the sequence [TA]7TAA), and 6/7 (heterozygous with one of each allele). Of the 110 infants, 10 (9%) had 7/7, 51 (46%) had 6/7, and 49 (45%) had 6/6 genotype; the differences between the three groups were not statistically significant. Also no differences were observed among different genotypes and mean serum total bilirubin concentrations. In conclusion, we showed that TA 7/7 and TA 6/7 genotypes are not rare in our population and that the presence of these polymorphisms alone does not play a significant role in the etiology of unexplained pathologic or prolonged neonatal hyperbilirubinemia.

To correlate the electroretinography (ERG) findings in patients with Duchenne/Becker muscular dystrophy (D/BMD) with the genotype and evaluate the ERG findings in DMD carriers.Fifteen deletion positive patients with DMD, two deletion positive patients with BMD and six DMD carriers in two families having a positive disease history were evaluated with DNA analysis, ophthalmologic and ERG findings.The mean age of the deletion positive D/BMD patients was 11.1 +/- 3.7 (range: 7-20). No abnormality was detected in the ophthalmic examination of the patients. In three out of 17 patients with D/BMD, ERG was normal whereas in 14 patients electronegative ERG was recorded in scotopic conditions. Mutational alterations observed in these three cases with normal ERG were located exceptionally at 5' hot spot; not like the others within central region. In all DMD carriers ERG findings were recorded as normal.ERG findings in D/BMD patients may show some correlations with molecular analysis, whereas it is not useful in DMD carriers.

We read the article entitled Familial Mediterranean fever gene mutation frequencies and genotype–phenotype correlations in the Aegean region of Turkey prepared by Ozalkaya et al. [1]. The results will be more rational while describing the characteristics of an inherited disease in a certain geographic region, if the data obtained from all or near all of the patients in that region is given. As being another center in the Aegean Region, serving children with familial Mediterranean fever (FMF), we compared our results with those of the above study and aimed to evaluate their consistency. There were 172 patients (M/F: 89/83) being followed up in our center with the diagnosis of FMF based on Tel Hashomer criteria. The mean ages at the onset of symptoms and at the time of diagnosis were months (1–292) and 115 § 63 months (2–612), respectively. Clinical features of the patients are shown in Table 1. MEFV gene analysis including 12 most frequent mutations seen in Turkish people was performed in 84 patients. The results are shown in Table 2. Most frequent mutation was M694V that was present in 60 (71.4%) patients. Three cases with amyloidosis had MEVF gene analysis; two cases were homozygous and one case was heterozygous for M694V mutation. There were 6 patients with none of the twelve mutations screened. The data of our cases from the same geographic region including the mean age of the patients at the diagnosis and at onset of the symptom, frequency of symptoms except for myalgia and genotypes of the patients were found similar to those described in the study of Ozalkaya et al. Although from the same region, myalgia was signiWcantly more frequent among our patients than those in the study of Ozalkaya et al. They categorized their patients due to reliability of diagnosis as deWnitive, probable and suspicious FMF groups. Myalgia frequency was reported to be 9, 7.8 and 2.4% in these subgroups, respectively, the diVerence among the groups being not statistically signiWcant. The rate of myalgia in their group was 6.1% in total, while 20.3% of our patients had myalgia [2–4]. Those patients with protracted febrile myalgia presented to our clinic mostly during the spring months, and their ASO levels were high [2, 3]. Most cases with myalgia were homozygous or compound heterozygous for M694V mutation, while only one case was homozygous for E148Q [2, 5]. One of the patients with myalgia had also amyloidosis and osteopoikilosis and he was transplanted for end stage renal disease [6].

Familial Mediterranean fever (FMF) is the most common autosomal recessive inherited inflammatory disease characterized by attacks of painful inflammation. Some patients with FMF have subclinical inflammation persisting between the attacks. We aimed to identify the demographic, clinical and genetic risk factors for subclinical inflammation in children with FMF. The medical records of the children with FMF were evaluated retrospectively for acute-phase response along with gender, age at the onset of symptoms and at the time of diagnosis, clinical signs and symptoms, the presence of amyloidosis and MEFV genotype. Patients with persistently elevated acute-phase response between the attacks were considered to have subclinical inflammation. Patients with or without subclinical inflammation (Group 1 and Group 2, respectively) were compared for the parameters defined above. Independent risk factors for subclinical inflammation were identified by multivariate logistic regression analysis. There were 105 children (male/female: 52/53) who were compliant on colchicine treatment. Subclinical inflammation was detected in 22 (20 %) patients. Group 1 had significantly higher rate of myalgia, arthritis/arthralgia, erysipelas like erythema, amyloidosis, protracted febrile myalgia and M694V mutation compared with Group 2. However, only the presence of myalgia and erysipelas like erythema were found to be independent risk factors for subclinical inflammation (OR 9.8 and 5.9, respectively). Children with FMF who have myalgia and erysipelas like erythema during the attacks are particularly at risk of ongoing inflammation and should be closely monitored for subclinical inflammation even during attack-free periods.