Insecticide imidacloprid influences cognitive functions and alters learning performance and related gene expression in a rat model.

The potential toxic effects of several pesticides, including imidacloprid on non-target organisms have not been clearly established. Also, the chronic effects of non-toxic doses on cognitive function in mammals are unknown. In this study, the effects of different doses of imidacloprid on learning and memory of infant and adult rats were evaluated, and the expressions of genes synthesizing proteins known to be associated with learning in brain tissues were also documented. 0.5, 2 and 8 mg/kg doses of imidacloprid were administered to newborn infant and adult Wistar albino rats by gavage. Their learning activities were evaluated, and the expression levels of the inotropic glutamate receptor GRIN1, synoptophysin, growth-associated protein 43 and the muscarinic receptor M1 in hippocampus were determined by real-time PCR method. Learning activities were diminished significantly at 2 and 8 mg/kg doses in the infant model groups and at 8 mg/kg dose in adult rats. Also, expression levels of GRIN1, SYP and GAP-43 were found to be insignificantly altered. Only the expression of M1 were significantly changed in high doses of adult group. Thus imidacloprid in high doses causes deterioration in cognitive functions particularly in infant rats, and this deterioration may be associated with changes in the expressions of related genes.

Family patterns of psychopathology in psychiatric disorders.

OBJECTIVE: Familial loading and crucial outcomes of family history of psychopathology in psychiatric disorders have long been recognized. There has been ample literature providing convincing evidence for the importance of family psychopathology in development of emotional disturbances in children as well as worse outcomes in the course of psychiatric disorders. More often, maternal psychopathology seems to have been an issue of interest rather than paternal psychopathology while effects of second-degree familiality have received almost no attention. In this study, we addressed the relations between affected first- and second-degree relatives of probands and categories of psychiatric disorders. METHOD: Subjects were 350 hospitalized psychiatric inpatients, consecutively admitted to psychiatry clinics in Van, Turkey. Mean age was 34.16 (SD±12) and 51.4% of the sample consisted of male patients. Assessment of psychopathology in psychiatric probands was conducted based on DSM-IV TR. Familial loading of psychiatric disorders amongst first- and second-degree relatives of patients were initially noted primarily relying on patients' retrospective reports, and confirmed by both phone call and following official health records via the Medical Knowledge System. We analyzed the data using latent class analysis approach. RESULTS: We found four patterns of familial psychopathology. Latent homogeneous subsets of patients due to familial characteristics were as paternal kinship psychopathology with schizophrenia, paternal kinship psychopathology with mood disorders, maternal kinship psychopathology and core family psychopathology. CONCLUSION: Family patterns were critical to exerting variation in psychiatric disorders of probands and affected relatives. Probands with a core family pattern of psychopathology exhibited the most colorful clinical presentations in terms of variation in psychopathology. We observed a specificity of intergenerational transmission of psychiatric disorders when family patterns of psychopathology were taken into consideration, even second-degree relatives of psychiatric probands.

Thermocouple and infrared sensor-based measurement of temperature distribution in metal cutting.

In metal cutting, the magnitude of the temperature at the tool-chip interface is a function of the cutting parameters. This temperature directly affects production; therefore, increased research on the role of cutting temperatures can lead to improved machining operations. In this study, tool temperature was estimated by simultaneous temperature measurement employing both a K-type thermocouple and an infrared radiation (IR) pyrometer to measure the tool-chip interface temperature. Due to the complexity of the machining processes, the integration of different measuring techniques was necessary in order to obtain consistent temperature data. The thermal analysis results were compared via the ANSYS finite element method. Experiments were carried out in dry machining using workpiece material of AISI 4140 alloy steel that was heat treated by an induction process to a hardness of 50 HRC. A PVD TiAlN-TiN-coated WNVG 080404-IC907 carbide insert was used during the turning process. The results showed that with increasing cutting speed, feed rate and depth of cut, the tool temperature increased; the cutting speed was found to be the most effective parameter in assessing the temperature rise. The heat distribution of the cutting tool, tool-chip interface and workpiece provided effective and useful data for the optimization of selected cutting parameters during orthogonal machining.

MicroRNA dysregulation in manic and euthymic patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BPD) is a major psychiatric disorder with an unclear pathophysiology. Peripheral blood samples are easily drawn, making them are good candidates for diagnosing diseases. MicroRNAs are small non-coding RNA transcripts that regulate gene expression by binding to the 3'- UTR of mRNAs and directing their degradation. The aim of this study was to use blood plasma to investigate microRNA dysregulations in bipolar manic and euthymic patients. SUBJECTS AND METHODS: Blood samples were collected from 58 patients with bipolar I disorder (19 manic, 39 euthymic) and 51 healthy controls. RESULTS: Four microRNAs (miR-29a-3p, p = 0.035; miR-106b-5p, p = 0.014; miR-107, p = 0.011; and miR-125a-3p, p = 0.014) were upregulated in the entire bipolar group, compared to the healthy controls. Seven microRNAs (miR-9-5p, p = 0.032; miR-29a-3p, p = 0.001; miR-106a-5p, p = 0.034; miR-106b-5p, p = 0.003; miR-107, p < 0.001; miR-125a-3p, p = 0.016; and miR-125b-5p, p = 0.004) were more upregulated in bipolar manic patients compared to the healthy controls, and two microRNAs (miR-106a-5p, p = 0.013, and miR-107, p = 0.021) showed statistically significant upregulation in the manic patients compared to the euthymic patients. CONCLUSIONS: Our results showed greater miRNA dysregulation in the manic patients than in the euthymic patients. Two microRNAs could be more selective for bipolar manic episodes. Future studies should include depressive patients along with euthymic and manic patients.

Peripheral Signatures of Psychiatric Disorders: MicroRNAs.

MicroRNAs (miRNAs) are 22 nucleotide long RNA transcripts, their synthesis starts in nucleus and continues in cytoplasm. As being critical for post-transcriptional regulators of gene expression they have been investigated in psychiatric disorders. There are numerous studies performed in peripheral tissues for psychiatric disorders. Here in this article, we aimed to review some common miRNAs denoted significant in at least two studies and their relevance to psychiatric research. We focused on miR-320, miR-106, miR-34, miR-223, miR-107, and miR-134.

Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder.

Vitamin D is implicated in several aspects of human physiology, and polymorphisms in the vitamin D receptor gene (VDR) are associated with a variety of neuropsychiatric disorders. The aims of this study are to determine whether VDR polymorphisms are associated with autism spectrum disorder (ASD), to examine serum 25-hydroxyvitamin D (25(OH)D) levels in ASD, and to explore whether VDR polymorphisms influence serum 25(OH)D levels. We investigated 480 subjects (237 children with ASD and 243 healthy controls) for the following VDR polymorphisms: TaqI, BsmI, FokI, ApaI, and Cdx2.Within the same samples, 25(OH)D levels were available only for 85 patients and 82 controls. The Cdx-2 variation was shown to deviate from Hardy-Weinberg equilibrium in the controls and was therefore excluded from the study. We found that the frequency of rare FokI TT, TaqI CC, and BsmI AA genotypes differed significantly between children with ASD and the controls (p=0.042, p=0.016, p=0.038, respectively). After correction for multiple testing, only the TaqI CC genotype remained significant. Further analysis using a recessive model showed that rare genotypes of these polymorphisms were significantly higher in patients compared to controls (p=0.045, p=0.005 and p=0.031, respectively). However, no significant association was found between ApaI and ASD. We found serum 25(OH)D levels to be significantly higher in children with ASD (p<0.001) and that the FokI polymorphism had an effect on serum 25(OH)D levels in children with ASD (p=0.041). Additionally, we found the haplotype GTTT (BsmI/TaqI/FokI/ApaI) conferred an increased risk for developing ASD (p=0.022; odds ratio [95% confidence interval]=2.322 [1.105-4.879]). This is the first clinical study evaluating the association between serum 25(OH)D levels and VDR polymorphisms in children with ASD. Our results demonstrated a significant association between TaqI, BsmI, and FokI polymorphisms and ASD and showed for the first time that FokI polymorphisms and haplotype GTTT (BsmI/TaqI/FokI/ApaI) are associated with an increased risk of ASD. Our findings support the hypothesis that 25(OH)D is involved in the pathophysiology of autism and that serum 25(OH)D levels may be affected by FokI polymorphisms in children with ASD. Our results should be considered as preliminary and needs confirmation by future studies.

Contribution of polymorphisms in ESR1, ESR2, FSHR, CYP19A1, SHBG, and NRIP1 genes to migraine susceptibility in Turkish population.

Migraine, a highly prevalent headache disorder, is regarded as a polygenic multifactorial disease. Single-nucleotide polymorphisms (SNPs) in the genes that involved in sex hormone metabolism may comprise risk for migraine, but the results of previous genetic association studies are conflicting. The aim of this study was to evaluate genetic variants in genes involved in oestrogen receptor and oestrogen hormone metabolism in a Turkish population. A total of 12 SNPs in the ESR1, ESR2, FSHR, CYP19A1, SHBG and NRIP1 genes were genotyped in 142 migraine cases and 141 nonmigraine controls, using a BioMark 96.96 dynamic array system. In addition, gene-gene interactions were analysed using generalized multifactor dimensionality reduction (GMDR) methods. According to GMDR analysis, our results indicated that there was a significant association between migraine and gene-gene interaction among the CYP19A1, FSHR, ESR1 and NRIP1. Single-gene variant analysis showed that a significant association was observed between the TT genotype of rs10046 and migraine susceptibility.When the analysis was performed only in women, the GG genotype of rs2229741 was different between migraineurs and controls.When the female migraine patients were divided into two groups, migraine related to menstruation (MRM) or migraine not related to menstruation (MNRM), GG genotype of rs726281 was significantly associated with MRM. These results suggested that rs10046 could play a potential role in migraine susceptibility in Turkish population. Also, the rare GG genotype of rs726281 appears to influence migraine susceptibility in a recessive manner in MRM subgroup of female patients. In addition, variant GG genotype of rs2229741 may reduce the risk of migraine in Turkish women.

Craniofacial Characteristics of Thalassemia Major Patients.

OBJECTIVE: Thalassemias major are the most common autosomal recessive disorders; they are characterized by anomalies in the synthesis of the beta chains of hemoglobin and are often associated with varying degrees of craniofacial anomalies. The purpose of this study was to evaluate the craniofacial dimensions of ß-thalassemia patients and to identify differences by comparing them to those of a control group. MATERIALS AND METHODS: The study comprised 43 thalassemia major patients and 26 age- and sex- matched healthy control subjects. Anthropometric measurements were performed in six different craniofacial regions (head, face, nose, mouth, eyes, and ears); a total of 23 craniofacial variables were measured. RESULTS: Craniofacial measurements in the regions of the face, nose, lips and mouth, and ears in the thalassemia major patient group yielded statistically significant differences compared to those in the control group (p<0.05). However, no statistically significant differences were observed in the measurements of the head and eye regions. CONCLUSION: The study increased our understanding of the craniofacial anatomy of thalassemia major patients and enabled us to obtain quantitative results.

Family History in Patients with Bipolar Disorder.

INTRODUCTION: In this study, we aimed to better understand the genetic transmission of bipolar disorder by examining the family history of patients. METHODS: Sixty-three patients with bipolar disorder and their families were included. The final sample comprised 156 bipolar patients and their family members. An inclusion criterion was the presence of bipolar disorder history in the family. The diagnosis of other family members was confirmed by analyzing their files, hospital records, and by calling them to the hospital. RESULTS: Sixty-five patients were women (41.6%) and 91 were men (58.3%) (ratio of men/women: 1.40). When analyzing the results in terms of the transition of disease from the mother's or father's side, similar results were obtained: 25 patients were from the mother's side and 25 patients were from the father's side in 63 cases. CONCLUSION: The results of our study support the fact that a significant relationship exists between the degree of kinship and the heritability of bipolar disorder and, furthermore, that the effect of the maternal and paternal sides is similar on the transmission of genetic susceptibility.

Association of brain-derived neurotrophic factor and nerve growth factor gene polymorphisms with susceptibility to migraine.

Migraine is one of the most common neurological diseases worldwide. Migraine pathophysiology is very complex. Genetic factors play a major role in migraine. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), play an important role in central nervous system functioning, development, and modulation of pain. This study investigates whether polymorphisms in the BDNF and NGF genes are associated with migraine disease in a Turkish case-control population. Overall, 576 subjects were investigated (288 patients with migraine and 288 healthy controls) for the following polymorphisms: rs6265(G/A), rs8192466(C/T), rs925946(G/T), rs2049046(A/T), and rs12273363(T/C) in the BDNF gene, and rs6330(C/T), rs11466112(C/T), rs11102930(C/A), and rs4839435(G/A) in the NGF gene using 5'-exonuclease allelic discrimination assays. We found no differences in frequency of the analyzed eight polymorphisms between migraine and control groups. However, the frequency of minor A alleles of rs6265 in BDNF gene was borderline significant in the patients compared with the healthy controls (P=0.049; odds ratios [ORs] [95% confidence intervals {CIs}] =0.723 [0.523-0.999]). Moreover, when the migraine patients were divided into two subgroups, migraine with aura (MA) and migraine without aura (MO), the minor TT genotype of rs6330 in NGF was significantly higher in MA patients than in MO patients (P=0.036) or healthy controls (P=0.026), and this disappeared after correction for multiple testing. Also, the rs6330*T minor allele was more common in the MA group than in the MO group or controls (P=0.011, ORs [95% CIs] =1.626 [1.117-2.365] or P=0.007, ORs [95% CIs] =1.610 [1.140-2.274], respectively). In conclusion, this is the first clinical study to evaluate the association between BDNF and NGF polymorphisms in migraine patients compared with health controls. Our findings suggest that the NGF rs6330*T minor allele might be nominated as a risk factor for developing aura in migraine disease. Our results should be considered as preliminary, and they need to be confirmed by future studies.

Association of Polymorphisms within the Serotonin Receptor Genes 5-HTR1A, 5-HTR1B, 5-HTR2A and 5-HTR2C and Migraine Susceptibility in a Turkish Population.

OBJECTIVE: Migraine, a highly prevelant headache disorder, is regarded as a polygenic multifactorial disease. Serotonin (5-HT) and their respective receptors have been implicated in the patogenesis. METHODS: We investigated the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptor gene polymorphisms and their association with migraine in Turkish patients. The rs6295, rs1300060, rs1228814, rs6311, rs6313, rs6314, rs6318, rs3813929 (-759C/T) and rs518147 polymorphisms were analyzed in 135 patients with migraine and 139 healthy subjects, using a BioMark 96.96 dynamic array system. RESULTS: We found no difference in the frequency of the analyzed eight out of nine polymorpisms between migraine and control groups. However, a significant association was found between the rs3813929 polymorphism in the promoter region of 5-HTR2C gene and migraine. Also, the allele of rs3813929 was more common in the migraine group. CONCLUSION: This result suggests that the 5-HTR2C rs3813929 polymorphism can be a genetic risk factor for migraine in a Turkish population.

Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case-control study.

Migraine pathogenesis involves a complex interaction between hormones, neurotransmitters, and inflammatory pathways, which also influence the migraine phenotype. The Mediterranean fever gene (MEFV) encodes the pyrin protein. The major role of pyrin appears to be in the regulation of inflammation activity and the processing of the cytokine pro-interleukin-1ß, and this cytokine plays a part in migraine pathogenesis. This study included 220 migraine patients and 228 healthy controls. Eight common missense mutations of the MEFV gene, known as M694V, M694I, M680I, V726A, R761H, K695R, P369S, and E148Q, were genotyped using real-time polymerase chain reaction with 5' nuclease assays, which include sequence specific primers, and probes with a reporter dye. When mutations were evaluated separately among the patient and control groups, only the heterozygote E148Q carrier was found to be significantly higher in the control group than in the patient group (P=0.029, odds ratio [95% confidence interval] =0.45 [0.21-0.94]). In addition, the frequency of the homozygote and the compound heterozygote genotype carrier was found to be significantly higher in patients (n=8, 3.6%) than in the control group (n=1, 0.4%) (P=0.016, odds ratio [95% confidence interval] =8.57 [1.06-69.07]). However, there was no statistically significant difference in the allele frequencies of MEFV mutations between the patients and the healthy control group (P=0.964). In conclusion, the results of the present study suggest that biallelic mutations in the MEFV gene could be associated with a risk of migraine in the Turkish population. Moreover, MEFV mutations could be related to increased frequency and short durations of migraine attacks (P=0.043 and P=0.021, respectively). Future studies in larger groups and expression analysis of MEFV are required to clarify the role of the MEFV gene in migraine susceptibility.

Frequency of mutations in Mediterranean fever gene, with gender and genotype-phenotype correlations in a Turkish population.

Familial Mediterranean fever (FMF) is the most common hereditary inflammatory periodic disease, characterized by recurrent episodes of fever, abdominal pain, synovitis and pleurisy. The aim of this study was to determine the frequency and distribution of Mediterranean fever (MEFV) gene mutations and to investigate the clinical characteristics and genotype-phenotype correlation in patients with FMF in Aydin, a province in western Anatolia, Turkey. Therefore, we retrospectively analysed MEFV gene mutations in 383 patients with suspected FMF and the clinical features of 327 among them. The MEFV gene mutations were investigated using the reverse dot-blot hybridization technique. We detected 26 different genotypes and 11 different mutations. The most common mutations in our cohort were p.M694V (41.15%), p.E148Q (20.35%), p.M680I(G/C) (12.39%) and p.R761H (9.73%). Abdominal pain (86.2%), fever (80.7%), arthralgia (57.2%), vomiting (36.1%), arthritis (34.6%), fatigue (31.5%), anorexia (22.9%) and chest pain (19.0%) were the most prevalent clinical features in our patients. This is the first study from Aydin in which the distribution of MEFV gene mutations and clinical features were evaluated in patients with FMF. We found that the most common mutation was p.M694V in our region, while the frequency of the p.R761H mutation was higher compared to other regions of Turkey with respect to extracted data from previous similar studies. Presented results supported the clinical findings in the literature that the homozygous p.M694V and compound heterozygous genotype were associated with more severe courses in FMF patients.

Comparison of plasma MicroRNA levels in drug naive, first episode depressed patients and healthy controls.

Major depression is the most common psychiatric disorder. The diagnosis of depression depends on a patient's subjective complaints, and the nature of the heterogeneous disorder. Thus, there is no known biomarker for depression to date. Previous research has indicated that microRNAs are dysregulated in bipolar disorder and schizophrenia. We aimed to investigate microRNA dysregulation in plasma samples of patients with major depression. Venous blood samples of 50 depressed patients and 41 healthy controls were collected and the quantification of microRNAs was established using qRT-PCR. We found miR-320a significantly downregulated and miR-451a significantly upregulated in depressed patients. We also found miR-17-5p and miR-223-3p upregulated, but not as significantly as miR-451a. Merging our results with previous published data shows that the blood miR-320 family may be a potential microRNA family dysregulated in major depression. Research should be performed on miR-320-related pathways and their relationship to depression. Additionally, miR-451a could serve as a candidate biomarker for depression based on the acting mechanism of ketamine. Studies targeting miR-451a levels before and after treatment could be helpful.

Rhizomelic Chondrodysplasia Punctata Type 1 Caused by a Novel Mutation in the PEX7 Gene.

Peroxisomes are involved in various metabolic reactions. Rhizomelic chondrodysplasia punctata (RCDP) type 1 is one of the peroxisomal biogenesis disorders caused by mutations in the PEX7 gene and is inherited in an autosomal recessive manner. We present a nine-year-old boy with skeletal abnormalities and dysmorphic facial appearance. The patient was born to parents who were first cousins. Very-long-chain fatty acids and pristanic acid levels were in the normal range, but an elevated phytanic acid level was detected by gas chromatography/mass spectrometry. The PEX7 gene was sequenced in the patient and his parents. A novel homozygous mutation, c.192delT (p.F64Lfs*10), was identified in the patient and was present in heterozygosity in both parents. In conclusion, the clinical presentation and peroxisome profile of the patient suggest that this novel mutation leads to RCDP type 1.

High frequency of E148Q sequence variation in children with familial Mediterranean fever in southeast Turkey.

OBJECTIVE: The aim of this study was to investigate the spectrum of Mediterranean fever (MEFV) gene mutations and genotype-phenotype correlation in children with familial Mediterranean fever (FMF) in southeast Turkey. METHODS: A total of 507 children (274 females) with FMF and MEFV gene mutation(s) were included. A 15-year retrospective evaluation was conducted; parameters analyzed were: age, sex, age at symptoms onset, age at FMF diagnosis, delay between symptoms onset and diagnosis, FMF attack symptoms, and response to colchicine. Disease severity scores were calculated and MEFV mutation analysis was performed via real-time PCR for the 6 most frequent mutations. Children with comorbid diseases or tested negative for MEFV gene mutations were excluded to provide homogeneity. RESULTS: A family history of FMF was found in 60.2% (n=305) of patients. The most common symptoms reported for FMF attacks were abdominal pain (98.0%), fever (93.9%) and arthralgia (47.3%); 75.0% of patients (n=380) were heterozygous, 14.2% were homozygous (n=72) and 10.8% were compound heterozygous (n=55).The following MEFV gene mutation alleles were identified: E148Q (40.1%), M694V (25.9%), V726A (15.8%), R761H (7.4%), M680I (6.8%), and P369S (4.1%). The M694V subgroup had the lowest mean age of disease onset and the highest mean disease severity score, whereas the E148Q group had later mean disease onset and the lowest mean disease severity score (p<0.05). CONCLUSION: The highest E148Q mutation frequency and milder disease in the course of FMF in our study population may be due to geographic and ethnic background dissimilarities of southeast Turkey.

The spectrum of MEFV gene mutations and genotypes in Van province, the eastern region of Turkey, and report of a novel mutation (R361T).

Familial Mediterranean fever (FMF) is the most common hereditary inflammatory periodic disease, characterized by recurrent episodes of fever and abdominal pain, synovitis, and pleuritis. The aim of this study was to determine the frequency and distribution of Mediterranean fever (MEFV) gene mutations in Van province of Eastern Anatolia and to compare them with the other studies from various regions of Turkey. Therefore, we retrospectively evaluated MEFV gene mutations in 1058 pediatric patients with suspected FMF. The MEFV gene mutations were investigated using Sanger sequencing and the multiplex minisequencing technique. We identified 37 different genotypes and 16 different mutations. The four most common mutations and allelic frequencies were M694V (36.50%), E148Q (32.77%), V726A (14.09%), and M694I (4.41%). M694V was the most common mutation, and the M694I frequency was found to be higher compared to studies from other regions of Turkey. In addition, we identified a novel missense mutation (R361T, c.1082G>C) in exon 3 of the MEFV gene in a 12-year-old boy, who had a typical FMF phenotype. In conclusion, this study evaluated the distribution of MEFV gene mutations in children with FMF as the first study conducted in Van province, Eastern Anatolia.

Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.

Development of the human nervous system involves complex interactions among fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families and homozygous loss-of-function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations.

Alta frecuencia de variación de la secuencia de la mutación E148Q en niños con fiebre mediterránea familiar en el sureste de Turquía / High frequency of E148Q sequence variation in children with familial Mediterranean fever in southeast Turkey

Objetivo: El objetivo de este estudio fue investigar el espectro de las mutaciones genéticas localizadas en el gen de la fiebre mediterránea (MEFV) y la correlación entre el genotipo y el fenotipo en niños con fiebre mediterránea familiar (FMF) en el sureste de Turquía. Métodos: En el estudio se incluyeron 507 niños (274 eran de sexo femenino) con FMF y mutaciones genéticas localizadas en el gen MEFV. Se realizó una evaluación retrospectiva de 15 años; y se analizaron los siguientes parámetros: edad, sexo, edad al inicio de los síntomas, edad al diagnóstico de la FMF, demora entre el inicio de los síntomas y el diagnóstico, síntomas de ataque de la FMF y respuesta a la colchicina. Se calcularon los índices de severidad de la enfermedad y se realizó el análisis de la mutación del genMEFV mediante PCR en tiempo real para las seis mutaciones más frecuentes. Con el fin de aportar homogeneidad, se excluyeron los niños con comorbilidades o con un resultado negativo en las pruebas de mutaciones del gen MEFV. Resultados: Se encontró que el 60,2% (n= 305) de los pacientes tenían antecedentes familiares. Los síntomas más frecuentes que manifestaron durante los ataques de FMF fueron dolor abdominal (98,0%), fiebre (93,9%) y artralgia (47,3%); el 75,0% de los pacientes (n= 380) eran heterocigotos; el 14,2% homocigotos (n= 72) y el 10,8% heterocigotos compuestos (n= 55). Se identificaron las siguientes mutaciones en los alelos del gen MEFV: E148Q (40,1%), M694V (25,9%), V726A (15,8%), R761H (7,4%), M680I (6,8%), y P369S (4,1%). En el subgrupo M694V se observó una edad media más joven de inicio de la enfermedad y un puntaje medio más alto de gravedad de la enfermedad, mientras que el grupo E148Q tuvo un inicio medio de enfermedad más tardío y un puntaje medio más bajo de severidad de la enfermedad (p <0,05). Conclusión: La frecuencia más alta de la mutación E148Q y la enfermedad más leve en la evolución de la FMF en la población de nuestro estudio quizás se deba a las diferencias étnicas del sureste de Turquía.

Objective: The aim of this study was to investigate the spectrum of Mediterranean fever (MEFV) gene mutations and genotype-phenotype correlation in children with familial Mediterranean fever (FMF) in southeast Turkey. Methods: A total of 507 children (274 females) with FMF and MEFV gene mutation(s) were included. A 15-year retrospective evaluation was conducted; parameters analyzed were: age, sex, age at symptoms onset, age at FMF diagnosis, delay between symptoms onset and diagnosis, FMF attack symptoms, and response to colchicine. Disease severity scores were calculated and MEFV mutation analysis was performed via real-time PCR for the 6 most frequent mutations. Children with comorbid diseases or tested negative for MEFV gene mutations were excluded to provide homogeneity. Results: A family history of FMF was found in 60.2% (n= 305) of patients. The most common symptoms reported for FMF attacks were abdominal pain (98.0%), fever (93.9%) and arthralgia (47.3%); 75.0% of patients (n= 380) were heterozygous, 14.2% were homozygous (n= 72) and 10.8% were compound heterozygous (n= 55).The following MEFV gene mutation alleles were identified: E148Q (40.1%), M694V (25.9%), V726A (15.8%), R761H (7.4%), M680I (6.8%), and P369S (4.1%). The M694V subgroup had the lowest mean age of disease onset and the highest mean disease severity score, whereas the E148Q group had later mean disease onset and the lowest mean disease severity score (p<0.05). Conclusion: The highest E148Q mutation frequency and milder disease in the course of FMF in our study population may be due to geographic and ethnic background dissimilarities of southeast Turkey.