Turkish Ancestry Research Articles

Quality of life in adult patients with Familial Mediterranean fever living in Germany or Turkey compared to healthy subjects: a study evaluating the effect of disease severity and country of residence

We assessed quality of life (QOL) and disease activity in patients with Familial Mediterranean fever (FMF) of Turkish ancestry living in Germany or Turkey and conducted a correlation with FMF disease activity. 40 FMF patients in Turkey (TR), 40 FMF patients in Germany (G) and 40 healthy controls in Germany (C) were included. QOL was evaluated with the short form of the World Health Organisation Quality of Life scale (WHOQOL-BREF). FMF disease activity was examined with the Pras score. Mean age was TR 30.5 ± 10.6, G 35.2 ± 10.2, C 34.6 ± 10.7. Of the 120 participants, 77 were female. FMF patients in TR and G had a significantly decreased QOL physical health domain compared to controls (TR 59.7 ± 18.8, G 60.4 ± 19.4, C 76.5 ± 14.6). Turkish FMF patients had a lower QOL environment domain compared to controls (TR 62.3 ± 17.5, G 69.7 ± 16.5, C 72.3 ± 13.5). In the other QOL domains, no significant differences were found. The differences in QOL were robust to a regression analysis. No significant correlation between QOL and FMF disease activity was found. German FMF patients had longer duration of disease, younger age at onset and longer delay from disease onset to colchicine treatment. A total of 5 of 40 German FMF patients were not taking colchicine (TR:0). Erythrocyte sedimentation rate was lowest in TR with significant difference between TR and G as well as G and C (TR 13.2 ± 10.3, G 27.8 ± 19.4, C 16.3 ± 12.8 mm/h). C-reactive protein did not differ between TR and G. FMF has an important impact on QOL physical health domain. No correlation between FMF disease activity and the WHOQOL-BREF could be found.

Familial Mediterranean fever in Germany: epidemiological, clinical, and genetic characteristics of a pediatric population

Familial Mediterranean fever (FMF) is an autoinflammatory disease and belongs to the heterogeneous group of hereditary recurrent fever syndromes (HRFs). The aims of the study were to determine the incidence of FMF in Germany and to describe the spectrum of pyrin mutations and the clinical characteristics in children. A prospective surveillance of children with HRF including FMF was conducted in Germany during a time period of 3 years by the German paediatric surveillance unit for rare paediatric diseases (ESPED). Monthly inquiries were sent to 370 children's hospitals (Clinic-ESPED, n1) and to 23 laboratories (Laboratory-ESPED, n2). Inclusion criteria were children ≤ 16 years of age, disease-associated pyrin mutations, and more than three self-limiting episodes of fever >38.5 °C with increased inflammation markers. In n1, 122 patients with FMF and 225 pyrin mutations were identified. Ninety-two of 122 (75 %) children were of Turkish origin. The minimum incidence of FMF was estimated to be 3 (95 % CI: 2.48-3.54) per 10(6) person-years in the whole children population and 55 (95 % CI: 46-66) per 10(6) person-years in Turkish children living in Germany. N1 U n2 amounted to 593 asymptomatic and symptomatic carriers of 895 mutations (overlap of 73 cases with 134 mutations). p.Met694Val (45 %), p.Met680Ile (14 %), p.Val726Ala (12 %), and p.Glu148Gln (11.5 %) were the most common pyrin mutations. Despite FMF being the most frequent of the HRFs, its incidence in Germany is low. Twenty-five to 50 FMF patients ≤ 16 years are newly diagnosed per year. The disease is most commonly observed in individuals of Turkish ancestry.

Familial Mediterranean Fever (FMF) - Disease Activity and Quality of Life (QOL) in Adult Patients of Turkish Ancestry Living in Turkey or Germany

Background: Paediatric FMF-patients living in Turkey show a higher proportion of severe disease compared to Turkish children born and raised in Germany1. Our aim was to assess differences in the course of FMF in adults living in Turkey and Germany. Methods: Adult patients suffering from FMF according to the Livneh criteria2 with Turkish ancestry were prospectively included in the study in two university hospitals in Ankara, Turkey(TR) and Herne, Germany(D). A structured interview and the Turkish WHOQOL-BREF were performed. Results: 61 patients were included (TR:31/D:30). The two groups were significantly different in the following aspects (mean±SD): percentage of patients on colchicine treatment (TR:100%/D: 83.3%,p=0.02), daily colchicine dosage in mg among patients taking colchicine (TR: 1.6±0.7/D:1.15±0.7,p=0.009), duration of disease (TR:15.5±9.5/D:22.4±8.2y,p=0.003). In other aspects examined there was no significant difference. The groups were similar in terms of age at study inclusion (TR:30.9±10.8/D:34.2±10.5y), age at onset of FMF symptoms (TR: 15.4±11.3/D:11.8±6.5y), female sex (TR: 74%/D:60%), FMF-severity according to the score by Pras et al.3(TR:6.6±2.3/D:6.4±1.9) and the 4 domains of the WHOQOL-BREF (expressed on a 0-100 scale) physical health (TR:57.5±19/D:59.1±20.4), psychological health (TR: 61.3±17.4/D:66.4±19.2), social relationship (TR:66.4±21.7/D:67±23.3), environment (TR: 62.2±18.4/D:68.5±16.8). There was no relevant and significant correlation between FMF-severity and QOL. Conclusion: 16.7 % of FMF-patients of Turkish origin living in Germany included in our study are not taking colchicine (TR: 0%). The average colchicine-dosage in Germany is lower and patients examined in Germany had a longer duration of disease. However, there was no significant difference in disease activity and QOL between FMF patients in the two nations. No relevant correlation between FMF disease severity and QOL could be found.

Assesing the Effect of ANA Positivity on Clinical Picture of the Juvenile Idiopathic Arthritis in a Large Cohort of Turkish Ancestry

Assesing the Effect of ANA Positivity on Clinical Picture of the Juvenile Idiopathic Arthritis in a Large Cohort of Turkish Ancestry

Fractured multiculturalism: Conflicting representations of Arab and Muslim Australians in Australian print media

Arab and Muslim migration is not new to Australia, where Muslims have lived for over 140 years, and are one of the fastest-growing minority groups (Ho, 2007). Despite stereotypes of a singular Arab or Muslim identity, Australia's Arab and Muslim populations comprise several ethnically diverse communities. The Human Rights and Equal Opportunity Commission (HREOC, 2004) states that the largest groups are those who identify as being of Lebanese (30%) and Turkish (18%) ancestry, with smaller, yet wellestablished groups of Afghans, Bosnians, Pakistanis and Indonesians. In addition to new arrivals from North Africa and the Middle East, numerous Arab and Muslim communities are second- and third-generation Australian. For example, 36 percent of Australian Muslims were born in Australia (HREOC, 2004).

Molecular features of 23 patients with glycogen storage disease type III in Turkey: a novel mutation p.R1147G associated with isolated glucosidase deficiency, along with 9 AGL mutations

Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency in the glycogen debranching enzyme (gene symbol: AGL) with two enzyme activities: transferase and glucosidase. A missense mutation causing isolated glucosidase deficiency has never been reported. In this study, we examined 23 patients of Turkish ancestry and identified a novel missense mutation p.R1147G with isolated glucosidase deficiency, along with nine AGL mutations: six nonsense mutations (p.W373X, p.R595X, p.Q667X, p.Q1205X, p.W1327X and p.Q1376X), one deletion (c.1019delA) and two splicing mutation (c.293+2T>G and c.958+1G>A). As p.R1147G impaired glucosidase activity, but maintained transferase activity in vitro, a 12-year-old girl homozygous for p.R1147G was diagnosed with having isolated glucosidase deficiency. Of nine other mutations, p.W1327X and c.1019delA were recurrent, whereas seven mutations were novel. Six patients with p.W1327X were all from two nearby cities on the East Black Sea and shared the same AGL haplotype, indicating a founder effect in Turkish patients. Patients with the same mutations had identical haplotypes. Our results provide the first comprehensive overview of clinical and molecular features of Turkish GSD III patients and the first description of the missense mutation associated with isolated glucosidase deficiency.

Isolated Unilateral Temporal Muscle Hypertrophy: A Rare Cause of Hemicranial Headache

A case of isolated unilateral hypertrophy of the Musculus temporalis identified by magnetic resonance imaging associated with recurrent hemicranial headache in a 22-year-old woman with Turkish ancestry is presented. Symptomatic relief was achieved by administration of acetaminophen. A review of the literature is presented and additional treatment options are discussed.

Hepatitis B Virus: Something Old, Something New

Hepatitis B Virus: Something Old, Something New

Lack of association between IL-1β/α gene polymorphisms and temporal lobe epilepsy with hippocampal sclerosis

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is one of the most common medically intractable epilepsy syndromes and the pathogenesis of HS remains highly obscure. Recent studies demonstrated controversial results about the relationship between interleukin (IL) gene polymorphism and epilepsy in different ethnic groups. This correlation was investigated in Turkish patients with MTLE-HS. The allele distribution of IL-1alpha and IL-1beta in 47 patients of Turkish ancestry was determined and compared with 99 ethnically matched control subjects. Analysis of genotype frequencies between patients and controls showed no statistically significant difference (p>0.05). Our data suggest that IL-1alpha and IL-1beta gene polymorphisms do not act as a strong susceptibility factor for MTLE-HS in individuals of Turkish ancestry.

Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7).

Mutations in the parkin gene have been identified as a common cause of autosomal recessive inherited Parkinson disease (PD) associated with early disease manifestation. However, based on linkage data, mutations in other genes contribute to the genetic heterogeneity of early-onset PD (EOPD). Recently, two mutations in the DJ1 gene were described as a second cause of autosomal recessive EOPD (PARK7). Analyzing the PARK7/DJ1 gene in 104 EOPD patients, we identified a third mutation, c.192G>C (p.E64D), associated with EOPD in a patient of Turkish ancestry and characterized the functional significance of this amino acid substitution. In the patient, a substantial reduction of dopamine uptake transporter (DAT) binding was found in the striatum using [(18)F]FP-CIT and PET, indicating a serious loss of presynaptic dopaminergic afferents. His sister, homozygous for E64D, was clinically unaffected but showed reduced dopamine uptake when compared with a clinically unaffected brother, who is heterozygous for E64D. We demonstrate by crystallography that the E64D mutation does not alter the structure of the DJ1 protein, however we observe a tendency towards decreased levels of the mutant protein when overexpressed in HEK293 or COS7 cells. Using immunocytochemistry in contrast to the homogenous nuclear and cytoplasmic staining in HEK293 cells overexpressing wild-type DJ1, about 5% of the cells expressing E64D and up to 80% of the cells expressing the recently described L166P mutation displayed a predominant nuclear localization of the mutant DJ1 protein.

Differential Effects of Parkinson's Disease-associated Mutations on Stability and Folding of DJ-1

Mutations in the PARK7/DJ-1 gene cause autosomal-recessive Parkinson's disease. In some patients the gene is deleted. The molecular basis of disease in patients with point mutations is less obvious. We have investigated the molecular properties of [L166P]DJ-1 and the novel variant [E64D]DJ-1. When transfected into non-neuronal and neuronal cell lines, steady-state expression levels of [L166P]DJ-1 were dramatically lower than wild-type [WT]DJ-1 and [E64D]DJ-1. Cycloheximide and pulse-chase experiments revealed that the decreased expression levels of [L166P]DJ-1 were because of accelerated protein turnover. Proteasomal degradation was not the major pathway of DJ-1 breakdown because treatment with the proteasome inhibitor MG-132 caused only minimal accumulation of DJ-1, even of the very unstable [L166P]DJ-1 mutant. Because of the structural resemblance of DJ-1 with bacterial cysteine proteases, we considered an autoproteolytic mechanism. However, neither pharmacological inhibition nor site-directed mutagenesis of the putative active site residue Cys-106 stabilized DJ-1. To gain further insight into the structural defects of DJ-1 mutants, human [WT]DJ-1 and both mutants were expressed in Escherichia coli. As in eukaryotic cells, expression levels of [L166P]DJ-1 were dramatically reduced compared with [WT]DJ-1 and [E64D]DJ-1. Circular dichroism spectrometry revealed that the solution structures of [WT]DJ-1 and [E64D]DJ-1 are rich in beta-strand and alpha-helix conformation. Alpha-helices were more susceptible to thermal denaturation than the beta-sheet, and [WT]DJ-1 was more flexible in this regard than [E64D]DJ-1. Thus, structural defects of [E64D]DJ-1 only become apparent upon denaturing conditions, whereas the L166P mutation causes a drastic defect that leads to excessive degradation.

Seven novel acid sphingomyelinase gene mutations in Niemann-Pick type A and B patients.

We have analyzed acid sphingomyelinase (SMPD1; E.C. 3.1.4.12) gene mutations in four Niemann-Pick disease (NPD) type A and B patients of Turkish ancestry and in three patients of Dutch origin. Among four NPD type A patients we found two homozygotes for the g.1421C > T (H319Y) and g.3714T > C (Y537H) mutations and two compound heterozygotes, one for the g.3337T > C (F463S) and g.3373C > T (P475L) mutations and the other for the g.84delC (G29fsX74) and g.1208A > C (S248R) mutations. One of the type B patients was homozygous for the g.2629C>T (P371S) mutation. The last two type B patients were homozygotes for the common g.3927_3929delCGC (R608del) mutation. The G29fsX74, S248R, H319Y, P371S, F463S, P475L and Y537H SMPD1 mutations are all novel and were verified by PCR/RFLP and/or ARMS. All of the identified mutations are likely to be rare or private, with the exception of R608del which is prevalent among NPD type B patients from the North-African Maghreb region. Geographical and/or social isolation of the affected families are likely contributing factors for the high number of homozygotes in our group.

Association of the platelet glycoprotein Ia C807T/G873A gene polymorphism and thrombosis in Behçet patients.

Thrombosis is a common complication of Behçet disease and the pathogenic mechanism of thrombotic tendency in Behçet disease is not well known. Several platelet membrane glycoprotein gene polymorphisms have been identified as risk factors for thrombosis. This study aimed to evaluate the possible role of the GP Ia C807T/G873A polymorphism as a risk factor for thrombosis in Behçet disease. We determined the prevalence of platelet glycoprotein Ia C807T/G873A gene polymorphism in Behçet patients. Genomic DNA was obtained from 20 patients with Behçet disease and 61 controls. All individuals were of Turkish ancestry and were genotyped for the GP Ia C807T/G873A polymorphism with real-time PCR method by LightCycler system. The 807 CC, CT and TT genotypes corresponded with 873 GG, GA and AA genotypes, respectively. Complete linkage between the 807 and 873 sites was found in all samples. The 807CC(873 GG), 807CT(873GA), 807TT(873AA) genotypes found to be 45.9%, 45.9% and 8.1% in controls and 30.0%, 55.0% and 15.0% in patients with Behçet disease, respectively. The Odds Ratio for BD (OR = 1.97; 95% confidence interval (CI): 0.42-9.13) is high for the 807 TT genotype compared with controls. Thrombosis was found in 7 cases of Behçet disease group: five cases have 807CT, one case has 807TT genotype and one case has 807CC genotype. Our data indicate hat patients with BD are affected by the glycoprotein Ia gene 807TT genotypes and carrying 807T allele. The risk of thrombosis is significantly higher in patients who have 807TT and 807CT genotypes than in patients who have 807CC genotype.

Plasma carnitine levels in children with Down syndrome.

Carnitine is responsible for several chemical processes, including lipid metabolism, nerve cell conduction, reduction in muscle hypotonia, and limitation in oxidative damage to cells. In patients with Down syndrome (DS), the process of growth is behind that of normal children and neuromuscular control is attained somewhat later. The purpose of this study was to assess variation in levels of carnitine in normal and DS children and the relationship between the amount of carnitine and age. The study involved 30 (15 girls, 15 boys) normal children and 40 (20 girls, 20 boys) DS patients of Turkish ancestry, 6 months to 13 years of age. Carnitine level was determined using Deufel's enzymatic method. Carnitine level was significantly lower in DS patients compared with normal children between 6 months to 5 years of age. Between 5 and 13 years of age, the level of carnitine was about the same in both the normal and DS groups. The results suggest that carnitine level shows a different pattern of age related increase in DS compared to normal children.

Mutation analysis in myophosphorylase deficiency (McArdle's disease).

Inherited deficiency of myophosphorylase leads to glycogen storage disease type V (McArdle's disease). We performed mutation analysis in 9 patients of eight unrelated families from Germany with typical clinical presentation of myophosphorylase deficiency. Beside previously described mutations we identified four novel mutations in the myophosphorylase gene. Four patients were homozygous for a nonsense mutation Arg49Stop that has been reported to be the most common mutation in white patients. Two affected siblings were compound heterozygotes for a novel missense mutation Gly685Arg and the nonsense mutation Arg49Stop. One patient carried a novel nonsense mutation Arg575Stop and a previously identified missense mutation Gly204Ser. In another patient, we identified a novel missense mutation Gln665Glu and a single-base deletion delA in Lys753. One patient of Turkish ancestry carried a newly identified homozygous A-to-G transition (ATG to GTG) abolishing the translation initiation codon of the myophosphorylase gene. These results suggest that Arg49Stop also is the most common genetic error associated with myophosphorylase deficiency in the German population. Our findings further demonstrate molecular heterogeneity of myophosphorylase deficiency among the clinically homogeneous patients we studied.

Glycogen Storage Disease type II: genetic and biochemical analysis of novel mutations in infantile patients from Turkish ancestry.

Glycogen Storage Disease type II (GSDII) is caused by the deficiency of lysosomal alpha-glucosidase (acid maltase). This paper reports on the characterization of the molecular defects in 6 infantile patients from Turkish ancestry. Five of the 6 patients had reduced levels of the lysosomal alpha-glucosidase precursor. Conversion to mature enzyme was impaired in all cases, and the lysosomal alpha-glucosidase activity in all patients fibroblasts was less than 0.5% of control. DNA sequence analysis revealed 3 new mutations. One mutation, found in 3 patients in homozygous form, was a double insertion in exon 19 (2471AG-->CAGG) leading to a frameshift after Pro 913. It is the first insertion mutation described in the lysosomal alpha-glucosidase gene. Two patients were homozygous for missense mutations leading to the substitution of Ser to Pro at amino acid 566 (S566P) in one case and of Pro to Arg at amino acid 768 (P768R) in the other. One patient was found to have a Gly to Arg missense mutation at amino acid 643 (G643R), previously identified in an adult patient (Hermans et al., 1993), combined with a silent second allele. The latter 3 mutations were introduced in the wild type lysosomal alpha-glucosidase cDNA and expressed in COS cells to analyze their effect. Precursor species of 110 kD were formed but the maturation was impaired. As a result there was an overall deficiency of catalytic activity, which is in accordance with the findings in the patients fibroblasts and with the clinical phenotype.

Glycogen storage disease type II: Genetic and biochemical analysis of novel mutations in infantile patients from Turkish ancestry

Glycogen storage disease type II: Genetic and biochemical analysis of novel mutations in infantile patients from Turkish ancestry

‘Der schlechteste Staat’: Ahmed Midhat Efendi (1844-1913) on Byzantine institutions

AbstractJust as Karl Marx, in 1842, called the Byzantine empire ‘der schlechteste Staat’, so did Ahmed Midhat Efendi (1844–1913), the protagonist of Ottomanism and at the same time the first Ottoman ‘to make a strong and clear case for the Turkish ancestry of the Ottomans’ (David Kushner), a few decades later. Byzantine history stands, according to Midhat, for the Dark Ages, and the Byzantine empire for corruption, lawlessness, extravagance and frivolity. By contrast, the picture drawn by him of the early Ottomans is one of a community based on high moral values such as decency, concord, obedience and mutual esteem. In his view, the rise of the Ottomans heralds the dawning of the Modern Age. His identification of the Ottomans as the liberators from the Dark Ages of all the peoples previously under Byzantine rule is the central element in his concept of the ‘enlightened and liberating Ottomans,. His Detailed History of Modern Times (Mufassal Tarih-i Kurun-i Cedide), with its section on Byzantine history an...