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BACKGROUND: Familial Mediterranean fever (FMF), an autosomal recessive, autoinflammatory disease that is common in Arabs, Jews, Armenians and Turks, is caused by mutations in the MEFV gene, which encodes a protein called pyrin. The disease is characterised by recurrent fever, peritonitis, pleuritis, abdominal pain and arthralgia. OBJECTIVE: Determine the distributions of MEFV mutations and their relationship with clinical manifestations. DESIGN: Retrospective, descriptive. SETTING: Turkish community. SUBJECTS AND METHODS: The study included patients with complaints related to FMF who were admitted to the research hospital of Cumhuriyet University between 2005 and 2017. FMF was diagnosed by physical examination using the Tel-Hashomer criteria. MEFV mutations were detected by reverse hybridization strip assay and pyrosequencing. MAIN OUTCOME MEASURE: The prevalence of specific MEFV gene mutations in a large cohort of Middle Anatolia. SAMPLE SIZE: 10 033 patients admitted, 1223 with confirmed mutations. RESULTS: Of 1684 patients diagnosed by Tel-Hashomer criteria, mutation screening confirmed that 1223 patients (72.6%) had FMF. Male/female ratio of the FMF patients was 1.3:1. One or more FMF mutations were found in 4497 patients (44.8%). 3262 had heterozygous or carrier mutations, 821 had compound heterozygous mutation, 381 had homozygous mutations, and 21 had triple mutations. Sixty-six percent had a family history of the disease and 13.7% of the patients had parental consanguinity. Main symptoms found in the patients were abdominal pain (85.2%), fever (84%), chest pain (30.2%), arthralgia (28.6%), rash or erysipelas-like erythema (8.2%). The most common mutation in this population was M694V (39%) of 5753 alleles. CONCLUSION: M694V was the most frequent mutation in our population (Middle Anatolia, Turkey) and cause severe forms of the disease. Patients with E148Q, V726A and R761H mutations may have milder FMF symptoms. There was a high rate of carriers in our study group. LIMITATIONS: Amyloidosis, an important complication of the disease, needs to be analyzed. CONFLICT OF INTEREST: None.
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Febre Familiar do Mediterrâneo/genética , Pirina/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Febre Familiar do Mediterrâneo/epidemiologia , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prevalência , Estudos Retrospectivos , Turquia/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: Chromosomal abnormalities are more common in the first trimester abortions. We aimed to investigate the types and prevalence of chromosomal abnormalities in couples with recurrent first trimester miscarriages in Sivas, Turkey. MATERIALS AND MEDHODS: Three hundred couples (600 individuals) who had a story of recurrent abortion were included in the study. Chromosome analysis was performed after the preparation of lymphocyte culture with the standard method. Karyotype analyses were supported by FISH and aCGH studies. RESULTS: Total 26 chromosome abnormalities (8.7%) were found in the couples (19 females and 7 males). Fifteen cases (57.7%) were structural anomalies and eleven cases (42.3%) were numerical chromosomal aberrations. We detected 5 balanced translocations (33.3%), 4 Robertsonian translocations (26.7%), 3 inversions (20%), 2 duplications (13.3%) and one deletion (6.7%) among the structural anomalies. Mosaic monosomy X in five cases (45.4%), the combination of mosaic monosomy-trisomy X in three cases (27.3%), the combination of mosaic monosomy-trisomy and tetrasomy X in two cases (18.2%) and mosaic pentasomy X in only one individual (9.1%) were encountered as numerical chromosome aberrations. 19 cases had heterochromatic changes or other chromosomal variations (satellite increments and inv9). CONCLUSION: Chromosome analysis in couples with recurrent miscarriage is necessary for possible preimplantation genetic diagnosis. As well as numerical and structural chromosome abnormalities, some chromosomal variations (heterochromatin and satellite increments etc.) may also contribute to recurrent miscarriages. Numerical chromosomal abnormalities are often associated with sex chromosomes and usually seen in females.
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Aborto Habitual/epidemiologia , Aborto Habitual/genética , Transtornos Cromossômicos/epidemiologia , Primeiro Trimestre da Gravidez , Aborto Habitual/diagnóstico , Adolescente , Adulto , Transtornos Cromossômicos/diagnóstico , Características da Família , Feminino , Humanos , Cariotipagem , Masculino , Gravidez , Prevalência , Estudos Retrospectivos , Turquia/epidemiologia , Adulto JovemRESUMO
PURPOSE: To present ocular findings and anterior segment-optical coherence tomography (AS-OCT) imaging findings of 2 cases of fish-eye disease (FED) involving 2 novel genetic variants of the lecithin-cholesterol acyltransferase (LCAT) gene. METHODS: A case report. RESULTS: A 46-year-old woman and 63-year-old man presented with blurred vision, burning sensation, and whitening of both eyes for 2 and 3 years, respectively. Ophthalmologic examination revealed slightly decreased visual acuity, yellowish-white diffuse corneal opacities causing corneal clouding, and dry eye disease bilaterally in both patients. AS-OCT imaging demonstrated diffuse hyperreflective corneal opacities predominantly located in the anterior stroma. On systemic examination, both patients had very low plasma high-density lipoprotein cholesterol levels. However, they did not have any systemic associations with familial LCAT deficiency or Tangier disease, which are differential diagnoses for corneal clouding and low plasma high-density lipoprotein cholesterol. Both patients were diagnosed with FED based on clinical findings. Furthermore, genetic analysis, in which novel variants of c.86A>G (p.Asn29Ser) in the first exon and c.1052A>G (p.Tyr351Cys) in the sixth exon on the LCAT gene were detected, confirmed the diagnosis. CONCLUSIONS: Although it is a rare genetic disorder, FED should be considered in the differential diagnosis of corneal clouding. Corneal lipid deposits, visible on AS-OCT are suggestive of FED, and genetic analysis can be used to confirm the clinical diagnosis. Finally, there may be a relationship between dry eye disease and LCAT enzyme deficiency disorders, which should be investigated in further studies.
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Opacidade da Córnea/diagnóstico , Deficiência da Lecitina Colesterol Aciltransferase/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fosfatidilcolina-Esterol O-Aciltransferase/genéticaRESUMO
INTRODUCTION: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is characterized by bladder distension without urinary tract obstruction, decreased or absent intestinal peristalsis and microcolon. Although the definitive cause remains unknown, changes in the ACTG2 gene are thought to be responsible for the intestinal and bladder hypoperistalsis. CASE REPORT: This female newborn with MMIHS had a c.532C>A /p.Arg178Ser heterozygous de novo mutation detected in the ACTG2 gene. Normal immature ganglion cells, normal calretinin punctate positivity, maintence of smooth muscle actin immunoreactivity, and decreased numbers of interstitial cells of Cajal(ICCs) were detected. CONCLUSION: This previously unreported c.532C>A /p.Arg178Ser heterozygous de novo mutation in the ACTG2 gene may lead to a severe form of MMIHS.
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Anormalidades Múltiplas/genética , Actinas/genética , Colo/anormalidades , Pseudo-Obstrução Intestinal/genética , Bexiga Urinária/anormalidades , Feminino , Humanos , Recém-Nascido , MutaçãoRESUMO
Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor (Serpine 1), and it inhibits both tissue plasminogen activator and urokinase plasminogen activator which are important in fibrinolysis. We aimed to find whether there is a possible association between PAI-1 level, PAI-1 4G/5G polymorphism, and endometrial cancer. PAI-1 levels in peripheral blood were determined in 82 patients with endometrial carcinoma and 76 female healthy controls using an enzyme-linked immunoassay (ELISA). Then, the genomic DNA was extracted and screened by reverse hybridization procedure (Strip assay) to detect PAI 1 4G/5G polymorphism. The levels of PAI-1 in the patients were higher statistically in comparison to controls (P < 0.001). The distribution of PAI-1 4G/5G polymorphism was quite different between patients and controls (P = 0.008), and 4G allelic frequency was significantly higher in the patients of endometrial cancer than in controls (P = 0.026). We found significant difference between Grade 1 and Grade 2+3 patients in terms of the PAI-1 levels (P = 0.047). There was no association between PAI-1 4G/5G polymorphism and the grades of endometrial cancer (P = 0.993). Our data suggest that the level of PAI-1 and PAI-1 4G/5G gene polymorphism are effective in the formation of endometrial cancer. PAI-1 levels are also associated with the grades of endometrial cancer.
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Neoplasias do Endométrio/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Inibidor 1 de Ativador de Plasminogênio/genética , Adulto , Idoso , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Genótipo , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Inibidor 1 de Ativador de Plasminogênio/biossíntese , Polimorfismo de Nucleotídeo Único , Regiões Promotoras GenéticasRESUMO
OBJECTIVE: Tinnitus is described as a disturbing sound sensation in the absence of external stimulation. We aimed to investigate whether there is any relationship between severe chronic tinnitus and angiotensin-converting enzyme (ACE) I/D and α-adducin (ADD1) G460W gene polymorphisms. MATERIALS AND METHODS: The patient group and control group consisted of 89 and 104 individuals, respectively. The evaluation of tinnitus was performed using the Strukturiertes Tinnitus-Interview (STI). The Tinnitus Handicap Inventory (THI) was used to evaluate the tinnitus severity. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used for genotyping. RESULTS: With regard to the ACE I/D polymorphism, there was no significant difference in genotype and allele frequencies between the patient group and control group. However, a statistically significant difference was found in genotype (p<0.01) and allele frequencies (p=0.021) of the ADD1 G460W gene polymorphism. Combined genotype analysis showed that the ACE II /ADD1 GW genotype was statistically significantly higher in the patient group than in the control group (X2: 7.15, p=0.007). The odds ratio value of the GW genotype was 2.5 (95% CI=1.4-4.7) (p<0.01). CONCLUSION: Our results demonstrate an association between ADD1 G460W gene polymorphism and susceptibility to severe chronic tinnitus. It was found that the GW genotype increased the disease risk by 2.5-fold compared with other genotypes. This indicates that ADD1 G460W polymorphism could be an important factor in the pathophysiology of tinnitus.
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Alelos , Proteínas de Ligação a Calmodulina/genética , Genótipo , Mutação INDEL/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético/genética , Zumbido/genética , Adulto , Idoso , Doença Crônica , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Zumbido/diagnóstico , TurquiaRESUMO
Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal alpha-galactosidase A (AGALA) activity. FD and familial Mediterranean fever (FMF) have typical clinical similarities, and both diseases may progress to end-stage renal diseases. In this study, we aimed to determine the prevalence of FD in patients with FMF from Central Anatolia of Turkey. The study group consisted of 177 FMF patients, followed up by the Adult and Pediatric Nephrology Clinic of Cumhuriyet University Hospital. Screening for AGALA activity was performed by the dry blood spot method. Mutation analysis for GLA gene was carried out for patients having an AGALA enzyme activity value lower than the normal reference value. Low AGALA activity was detected in 23 (13 %) patients. Heterozygous GLA gene mutation c.[937G>T] p.[D313Y] was detected in one female patient (0.56 %). The patient was a 53-year-old female with proteinuria and who had undergone left nephrectomy; her glomerular filtration rate (GFR) by scintigraphy was found to be 70 ml/min. She had M694V mutation and no clinical manifestation of FD. In our study, the prevalence rate of FD was found as 0.56 % in FMF patients. The similarities between the symptoms of FMF and FD might lead to a diagnostic dilemma in physicians at countries where FMF is observed frequently. Although the prevalence of FD is rare, physicians should keep in mind that FD has an ambiguous symptomology pattern of FMF.
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Doença de Fabry/epidemiologia , Febre Familiar do Mediterrâneo/genética , Mutação , alfa-Galactosidase/genética , Análise Mutacional de DNA , Doença de Fabry/genética , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/patologia , Feminino , Humanos , Masculino , Prevalência , Pirina/genética , Turquia/epidemiologiaRESUMO
BACKGROUND: 14q duplications caused by parental pericentric inversion of chromosome 14 are rarely reported and no clear genotype-phenotype correlation has been determined yet. CASE PRESENTATION: Here we reported a 7 years old female patient with recombinant chromosome characterized by 14 q duplication and originated from maternal pericentric inversion of chromosome 14. Principal clinical findings of the child include developmental delay, microcephaly, hypertelorism, low set ears, clinodactyly of fifth fingers, hypotonia, telecanthus and cardiac malformation. CONCLUSIONS: Her final karyotype was 46,XX,rec(14)dup(14q)inv(14)(p11.2q24)mat,arr14q24.1-qter(64,800,000-108,350,000 bp)x3.
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BACKGROUND AND AIM: There is an increased mortality risk in long-term hemodialysis patients of renal failure due to the chronic inflammation. The relationship between the chronic renal failure (CRF) and the role of familial genetic markers remains incompletely understood. In the current study, it was aimed to find out the prevalence of common MEFV gene mutations and BcII polymorphism in serum amyloid A1 (SAA1) gene in chronic renal patients (CRF) who require long-term hemodialysis. METHOD: Current cohort includes 242 CRF patients and 245 healthy individuals from the same population. Total genomic DNA was isolated from peripheral blood-EDTA samples and genotyping of target MEFV gene was carried out by reverse hybridization Strip Assay and real-time techniques. The SAA1 gene was genotyped by the BclI-RFLP method. RESULTS: Increased mutated MEFV genotypes were found in current CRF patients when compared with the control group from the same ethnicity and the difference was statistically significant (Table 2) (OR: 4.9401, 95% CI: 3.0694-7.9509), p<0.0001. The most frequent point mutations were M694V and E148Q. The mutated T allel frequency in the SAA1 gene was also different when compared with the healthy controls and the difference was found to be statistically significant (χ2: 13.18; p=0.000). CONCLUSIONS: The current results indicate the germ-line mutations in both genetic biomarkers (MEFV and SAA1 genes) that are related to inflammation and amyloidosis processes may play a crucial role in CRF pathogenesis due to the long-term chronic inflammation.
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Amiloidose , Proteínas do Citoesqueleto/genética , Inflamação , Falência Renal Crônica , Diálise Renal , Proteína Amiloide A Sérica/genética , Adulto , Idoso , Amiloidose/etiologia , Amiloidose/metabolismo , Feminino , Marcadores Genéticos , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Falência Renal Crônica/genética , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único , Pirina , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Tempo , TurquiaRESUMO
OBJECTIVE: A number of chemokines and chemokine receptors are produced by intrinsic renal cells as well as by infiltrating cells during renal inflammation. The CCR2 chemokine receptor mediates leukocyte chemoattraction in the initiation and amplification phase of renal inflammation. The polymorphism, CCR2-V64I, changes valine 64 of CCR2 to isoleucine. We aimed to determine the frequency of CCR2-V64I polymorphism in patients with chronic renal failure requiring long-term hemodialysis. METHODS AND PATIENTS: The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the gene frequencies of CCR2-641 in CRF patients (n=210) and healthy controls (n=139) in the current study. RESULTS: The frequencies of the CCR2 genotype were 0.68 for V/V, 0.28 for V/I, and 0.4 for I/I in the CRF patients and 0.81 for V/V, 018 for V/I and 0.1 for I/I in healthy controls. The distribution of the CCR2-V64I mutant genotype was significantly different between subjects with CRF and healthy control subjects (X2=7.197 and p=0.027). CONCLUSION: We found that the CCR2-V64I polymorphism was significantly high in CRF patients. In addition to the contribution to disease pathogenesis, it was recently found that chemokines have therapeutic importance in chronic renal failure. The frequency of CCR2-V64I and other chemokine and chemokine receptor polymorphisms in renal pathologies must be further investigated in larger study populations and in different renal diseases.
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Falência Renal Crônica/genética , Falência Renal Crônica/terapia , Polimorfismo Genético/genética , Receptores CCR2/genética , Diálise Renal/tendências , Adulto , Idoso , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Isoleucina/genética , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Valina/genéticaRESUMO
The Familial Mediterranean Fever (FMF) shows an autosomal recessive pattern of inheritance and affects certain ethnic groups. Disease is caused by mutations in MEFV gene and more than 180 mutations have been defined in affected individuals. Current study aimed to determine the frequency-type of the mutations for MEFV gene in Sivas-middle Anatolian city. The cohort was composed of 3340 patients. MEFV gene mutations were studied by multiplex PCR based reverse hybridization stripAssay method. Patients' clinical features were; family history: 68%, erysipelas-like erythema: 17.6%, fever: 89.9%, abdominal pain: 84.2%, peritonitis: 90.2%, arthritis: 33%, pleuritis: 14.2%, parental consanguinity: 21.2%. Current results revealed that M694V is the most frequent mutation (43.12%), followed by E148Q (20.18), M680I(G/C) (15.00%) and V726A (11.32%). The study population has a high rate of carriers and the E148Q mutation frequency was found to be highest when compared to the other regions of Turkey and other Mediterranean groups.