<abstract xml:lang="en"><title style='display:none'>48, XXXX, A Rare Aneuploidy</title>The 48, XXXX chromosome constitution is a rare aneuploidy which shows some peculiar manifestations in affected females. This first report from India of tetrasomy X with bilateral, typical, complete coloboma of iris, shows the importance of chromosomal investigation and fluorescent <italic>in situ</italic> hybridization (FISH) in females with mental retardation and dysmorphic features.</abstract>

Centre for Genetic Disorders, Guru Nanak Dev University, Amritsar, 143005, India

Medical Service Provider, Rudhiana, Gurdaspur, India

48, XXXX, A Rare Aneuploidy

Macedonian Academy of Sciences and Arts, Research Center for Genetic Engineering and Biotechnology “Georgi D. Efremov,” Skopje, Republic of Macedonia

Clinic of Endocrinology and Metabolic Disorders, Faculty of Medicine, Skopje, Republic of Macedonia

Genetic Causes of Male Infertility

<abstract xml:lang="en"><title style='display:none'>Thalassemias and Other Hemoglobinopathies in Former Yugoslavia</title>This review summarizes our results on the epidemiology and molecular basis of thalassemias and other hemoglobinopathies in the republics and provinces of the Former Yugoslavia. Over the past 40 years, surveys of more than 37,000 school children and more than 1,600 adults, from all over Former Yugoslavia, except Slovenia, have shown an average incidence of β-thalassemia (β-thal) trait of 1.2%, ranging from 2.9% in the south (Macedonia) to 0.8% in the northwest (Croatia). The frequency of δβ-thal was 0.2%, while that of Swiss type hereditary persistence of fetal hemoglobin (HPFH) was 0.4%. Screening of 12,680 newborns has shown that the frequency of α-thal trait was 1.5%. The molecular basis of the thalassemias in the populations of Former Yugoslavia has been completely defined. More than 700 β-thal chromosomes have been studied and their molecular defect was determined. In the Macedonian population, 16 different β-thal mutations were detected, four of which (IVS-I-110, G→A; IVS-I-6, T&gt;C; IVS-I-1, G&gt;A and codon 39, C&gt;T) accounted for 85% of all β-thal chromosomes. In the Croatian population, 18 different β-thal alleles were detected. Four new mutations [nucleotide (nt) -87, C&gt;A; IVS-II-850, G&gt;C; initiation codon mutation T&gt;C; polyadenylation signal (poly A), AAT<italic>A</italic>AA&gt;AAT<italic>G</italic>AA)] and one new deletion (1605 bp), were characterized. Molecular analyses of DNA from over 50 unrelated cases with δβ-thal have shown that this condition was mainly caused by a 13 kb deletion (Sicilian type); in one family, a deletion of &gt;18 to 23 kb (Macedonian-Turkish type), and in another, a deletion of 148 kb (Yugoslavian type of εγδβ-thal) of the β-globin gene complex, were discovered. Molecular analyses of α-thal from Former Yugoslavia revealed the following defects: the -20.5, -17.5 and -3.7 kb deletions, a 5 nt deletion, and Hb Icaria [α142, Term→Lys (T<italic>A</italic>A&gt;T<italic>C</italic>A in α2)]. The incidence of abnormal hemoglobins (Hbs) in Former Yugoslavia was 0.3%. Five different α chain variants in 16 families, 16 different β chain variants in 61 families, one δ chain variant in one family, two types of Hb Lepore in 122 families and two γ chain variants, have been characterized.</abstract>

Thalassemias and Other Hemoglobinopathies in Former Yugoslavia

<abstract xml:lang="en"><title style='display:none'>Hypergonadotropic Hypogonadism, Progressive Early-Onset Spinocerebellar Ataxia, and Late-Onset Sensorineural Hearing Loss: Case Report and Literature Review</title>The association of ataxia, hypergonadotropic hypogonadism and hearing loss is extremely rare. Considerable heterogeneity exists in the literature of the neurological manifestations, age of onset, clinical severity and associated abnormalities. We describe a 24-year-old woman with secondary hypergonadotropic amenorrhea, early-onset progressive spinocerebellar ataxia (SCA), late-onset sensorineural hearing loss and normal intelligence and compare it with reported cases.</abstract>

Centre for Reproductive Medicine, Zekai Tahir Burak Women's Health Research and Education Hospital, Ankara, Turkey

Department of Neurology, Zekai Tahir Burak Women's Health Research and Education Hospital, Ankara, Turkey

Hypergonadotropic Hypogonadism, Progressive Early-Onset Spinocerebellar Ataxia, and Late-Onset Sensorineural Hearing Loss: Case Report and Literature Review

<abstract>
<title style='display:none'>Abstract</title>
L-2-hydroxyglutaric aciduria (L2HGA), which is a rare autosomal recessive metabolic disorder caused by mutations in the encoding <italic>L2HGDH</italic> gene. Neurological symptoms are the main predominant clinical signs. The distinctive feature is the specific multifocal lesion of the white matter detected on magnetic resonance imaging (MRI). A 7-year-old male patient of Turkish origin was admitted to the hospital because of hand tremors. Physical examination revealed macrocephaly, intention tremors, walking disability and ataxic gait. Urine organic acid analysis showed increased excretion of L-2-hydroxyglutaric acid (L2HG acid). Analysis of the <italic>L2HGDH</italic> gene revealed a novel homozygous c.368A&gt;G, p. (Tyr123Cys) mutation. L-2-hydroxyglutaric aciduria is a cerebral organic aciduria that may lead to various neurological complications. Early recognition of symptoms of L2HGA is important for initiation of supportive therapy that may slow down the progression of the disease.</abstract>

A 7-year-old boy with hand tremors and a novel mutation for L-2-hydroxyglutaric aciduria

<abstract xml:lang="en"><title style='display:none'>Wolf-Hirschhorn Syndrome: Report of two Cases in Bosnia and Herzegovina</title>Wolf-Hirschhorn syndrome (WHS) is a rare developmental disorder caused by a partial deletion of the short arm of chromosome 4 (4p-). The main phenotypic characteristics of WHS are: intrauterine growth retardation, mental retardation, typical facial dysmorphism, microcephaly and midline fusion defects (cleft lip or palate, cardiac septal defects). Other abnormalities, such as agenesis of the corpus callosum, dysplastic kidneys, iris coloboma and skeletal abnormalities have occasionally been described.We describe two female newborn babies with a 4p deletion, who have a majority of the main phenotypic features of WHS. Prenatal diagnosis of the syndrome is very important, because dysmorphologic features are associated with profound mental retardation. Postnatal recognition of the syndrome requires genetic counseling of the parents and supportive multidisciplinary treatment.</abstract>

Pediatric Clinic of Clinical University Center Sarajevo, 71 000 Sarajevo, Bosnia and Herzegovina

Institut for Human Genetics Sarajevo, Medical Faculty, University of Sarajevo, 71 000 Sarajevo, Bosnia and Herzegovina

Wolf-Hirschhorn Syndrome: Report of two Cases in Bosnia and Herzegovina

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Background</title>Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development characterized by numerous developmental anomalies that are restricted to the head and neck. Most TCS cases are inherited in an autosomal dominant manner. The diagnosis of TCS relies on clinical and radiographic findings. The four genes involved in TCS are <italic>TCOF1</italic>, <italic>POLR1D, POLR1C,</italic> and <italic>POLR1B</italic>.</sec>
<sec><title style='display:none'>Case presentation</title>In this report, we present the case of a 7-year-old Moroccan boy who exhibited distinctive dysmorphic features, including coloboma and zygomatic bone hypoplasia. Upon genetic analysis, a mutation in the <italic>TCOF1</italic> gene was identified, conclusively confirming the presence of Treacher Collins Syndrome. It is worthy that the correct etiological diagnosis was significantly delayed due to the initial misperception that the observed malformation syndrome was a result of drug teratogenicity.</sec>
<sec><title style='display:none'>Conclusions</title>This case highlights the importance of seeking pharmacovigilance advice if any adverse event occurs following medication use. Furthermore, requesting a genetic consultation to establish a confirmed etiological diagnosis for any malformation syndrome can significantly reduce the protracted social and psychological suffering that patients and their families may endure.</sec>
</abstract>

Misdiagnosis of Tracher-Collins Syndrome Initially Attributed to Drug Teratogenicity: A Moroccan Case Report

<abstract>
<title style='display:none'>Abstract</title>
Raynaud-Claes syndrome is rare condition characterized with intellectual disability and is caused by X-linked pathogenic variants in <italic>CLCN4</italic> gene. Hemizygous missense variant NM_001830.4: c.1597G&gt;A (p.V533M) was detected in a 6-year-old male followed up with intellectual disability, dysmorphism, and epileptic encephalopathy. The mother and one sister of the patient were also carrying the same variant. The clinical picture of the patient was significantly more severe, and the patient exhibited nonconvulsive status. Tonic status was observed with benzodiazepine treatment and the patient was successfully treated with a ketogenic diet. Many types of seizures can be seen in Raynaud-Claes syndrome, some of which can be life-threatening. <italic>CLCN4</italic> variants can be investigated in patients who exhibit an increase in tonic seizures with benzodiazepine treatment. However, ketogenic dietary therapy as first-line treatment can be lifesaving in resistant epilepsy cases caused by the <italic>CLCN4</italic> gene.
</abstract>

Experience with the Ketogenic Diet in a Boy with <italic>CLCN4</italic> Related Neurodevelopmental Disorder

<abstract>
<title style='display:none'>Abstract</title>
Chromosomal abnormalities are the most common causes of early pregnancy losses (EPLs). In this study, we aimed to evaluate the incidence and spectrum of chromosomal abnormalities in EPLs and correlate them with different clinical characteristics. We performed Quantitative Fluorescent PCR (QF-PCR), followed by subtelomeric Multiplex Ligation Probe Amplification (MLPA) analysis to detect chromosomal abnormalities in 900 products of conceptions (POCs) from EPLs collected over a period of 10 years.
Chromosomal abnormalities were present in 56.25% of uncontaminated EPLs, with significantly higher incidence in women ≥36 years (71.37%, p&lt;0.0001) in comparison to women ≤30 years of age (43.40%). Trisomies were also more common in women ≥36 years (79.68%, p&lt;0.0001) than in those ≤30 years of age (48.70%). In contrast, triploidy and monosomies were more prevalent in women ≤30 years of age (26.09%, p&lt;0.0001 and 16.52%, p=0.0066 respectively) than in women ≥36 years of age (6.42% and 6.42% respectively). Trisomy 16 was more common in women ≤30 (39.29%, p=0.0009) than in those ≥36 years of age (16.78%), while trisomy 22 was predominant among women ≥36 (23.49%, p=0.013), and was not present in the group of women ≤30 years of age. The frequency of chromosomal abnormalities in POCs from women with sporadic (61.19%) was higher than in those with recurrent EPLs (55.21%). This difference, however, was not statistically significant (p=0.164). Although some differences in the chromosomal aneuploidy rates among women with different ABO blood groups, as well as among 6–8 and 9–11 gestational week EPLs were observed, further larger studies are required to confirm these findings.
In conclusion, our study enriches the knowledge about chromosomal abnormalities as a cause of EPLs and confirms the higher incidence of foetal chromosomal abnormalities in EPLs in women of older reproductive age. Furthermore, it shows that using QF-PCR and MLPA methodologies, a high detection rate of chromosomal abnormalities in EPLs can be reached.
</abstract>

Chromosomal Abnormalities in Early Pregnancy Losses: A Study of 900 Samples

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Introduction</title>The polymorphism of the angiotensin-converting enzyme (ACE) gene and interleukin-1 beta (IL-1b) gene could be associated with resistance in the treatment of anemia in dialysis patients with recombinant human erythropoietin (rHuEPO). The aim of the study was to evaluate the association between the polymorphism of the ACE and IL-1b genes and the response to rHuEPO therapy in dialysis patients with anemia.</sec>
<sec><title style='display:none'>Material and methods</title>The study investigated 69 patients on dialysis with anemia treated with recombinant human erythropoietin for 12 months. Genotyping of ACE and IL-1b polymorphism was done in all study patients at the initiation of the study. The patient’s demographic characteristics, dialysis vintage, and laboratory parameters were also evaluated as factors associated with rHuEPO resistance. The erythropoietin resistance index (ERI) was calculated as the weekly rHuEPO dose per kg of body weight, divided by the hemoglobin (Hb) concentration in g/dl.</sec>
<sec><title style='display:none'>Results</title>The Hb ≥ 110 g/l was registered in 37 (53.6%) patients. Patients with Hb ≥ 110 g/l were characterized by significantly higher serum levels of albumin, cholesterol, and iron than those with Hb &lt; 110 g/l. The serum level of the CRP, the weekly dose of rHuEPO, and ERI were significantly higher in patients with Hb &lt; 110 g/l compared to patients with Hb ≥ 110 g/l. The ERI value of ≥ 10 IUkg/weekly/g/dl was present in 27 (39.1%) patients. The serum levels of ferritin and CRP, and weekly dose of rHuEPO were significantly higher in patients with ERI value ≥ 10 IU kg/weekly/g/dl compared with the patients with ERI value &lt; 10 IUkg/weekly/g/dl. There was no significant association between the ERI and polymorphism of the ACE and IL-1b genes in study patients.</sec>
<sec><title style='display:none'>Conclusion</title>The polymorphism of the ACE and IL-1b genes was not significantly associated with the response to erythropoietin therapy in dialysis patients with anemia. Iron deficiency, malnutrition, and inflammation were factors associated with anemia and resistance to erythropoietin therapy in dialysis patients.</sec>
</abstract>

Association Between the Polymorphism of Angiotensin-Converting Enzyme Gene and Interleukin-1 Beta Gene and the Response to Erythropoietin Therapy in Dialysis Patients with Anemia

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Introduction</title>Pathogenic variants in <italic>TARS2</italic> are associated with combined oxidative phosphorylation deficiency 21 (COXPD21), an autosomal recessive disorder usually presenting as mitochondrial encephalomyopathy. Kidney impairment has been documented in a minority of COXPD21 patients, mostly with distal renal tubular acidosis.</sec>
<sec><title style='display:none'>Case report</title>We report on the first COXPD21 patient with generalized tubular dysfunction and early childhood progression to chronic kidney disease (CKD). Thorough diagnostic evaluation was initiated at six months of age due to failure to thrive, muscular hypotonia, motor delay and recurrent bronchiolitis. The boy was lost to follow-up until the age of two years, when he was readmitted with elevated creatinine level, reduced estimated glomerular filtrate rate, normochromic anaemia, metabolic acidosis and hyperkalaemia. Urine abnormalities pointed to generalized tubular dysfunction. Two novel heterozygous missense variants in <italic>TARS2</italic> gene were detected by the means of whole exome sequencing: c.1298T&gt;G (p.Phe438Cys) of maternal origin and c.1931A&gt;T (p.Asp644Val) of paternal origin. Currently, at 4.5 years of age, the boy has failure to thrive, severe motor and verbal delay and end stage of CKD. We referred the patient to paediatric centre that provides renal replacement therapy.</sec>
<sec><title style='display:none'>Conclusion</title>The overall clinical course in the patient we report on corresponds well to the previously reported cases of <italic>TARS2</italic> related COXPD21, especially in regard to neurological and developmental aspects of the disease. However, we point out the generalized tubulopathy and early occurrence of CKD in our patient as atypical renal involvement in COXPD21. Additionally, this is the first report of hypothyroidism and hypoparathyroidism in a COXPD21 patient.</sec>
</abstract>

Day Care Hospital, Mother and Child Health Care Institute of Serbia “Dr Vukan Čupić”

Expanding the Phenotypic Spectrum: Chronic Kidney Disease in a Patient with Combined Oxidative Phosphorylation Defect 21

<abstract>
<title style='display:none'>Abstract</title>
<sec><title style='display:none'>Background</title>Almost 50% of NSCLC patients who initially show a successful response to tyrosine kinase inhibitors targeted therapy (TKI therapy) eventually develop acquired <italic>EGFR</italic> T790M mutation. The T790M secondary mutation can cause resistance to the targeted therapy and disease relapse. Since this mutation can be present at very low frequencies in liquid biopsy samples, droplet digital PCR (ddPCR), due to its high sensitivity, has opened the possibility for minimally invasive monitoring of the disease during TKI targeted therapy.</sec>
<sec><title style='display:none'>Materials and methods</title>For this study, a total of 45 plasma samples from NSCLC patients with previously detected <italic>EGFR</italic>-activating mutations were analyzed. Extracted circulating free DNA was amplified and examined for the presence of T790M mutation using ddPCR technology. For the data analysis, QuantaSoft Software was used.</sec>
<sec><title style='display:none'>Results</title>Of 45 tested plasma samples, a total of 14 samples were identified as positive for the T790M mutation. The same samples eventually showed the presence of T790M mutation in FFPE. Droplet digital PCR showed its great advantage in high sensitivity detection of rare allele variants. Our ddPCR assay detected T790M mutant allele in frequencies from 0.1%. The average number of droplets generated by ddPCR was 9571.</sec>
<sec><title style='display:none'>Conclusion</title>Monitoring of the T790M mutation has an important role in the examination of the effects of the prescribed TKI therapy. Since monitoring of potential changes during TKI therapy requires repeated sampling, our results showed that ddPCR technology has made it possible to use liquid biopsy as an adequate minimally invasive alternative for single nucleotide polymorphisms (SNP) detection.</sec>
</abstract>

Droplet Digital PCR as a Molecular Tool for the Detection of the <italic>EGFR</italic> T790M Mutation in NSCLC Patients with the <italic>EGFR</italic> Activating Mutations

<abstract><title style='display:none'>Abstract</title> The presence of variable degrees of non progressive cognitive impairment is recognized as a clinical feature of patients with Duchenne and Becker muscular dystrophies (DMD and BMD), but its pathogenesis still remains a matter of debate. A number of findings have proved that rearrangements located in the second part of the dystrophin (DMD) gene seem to be preferentially associated with cognitive impairment. Dp140 is a distal dystrophin isoform, mainly expressed during fetal brain development, whose role for neuropsychological functioning was suggested. The aims of the current study were to explore the possible association between cognitive impairment and DNA mutations affecting the regulatory regions of Dp140, as well as to compare the neuropsychological functioning of patients affected with DMD and Intermediate muscular dystrophy (IMD) with those affected by Becker muscular dystrophy (BMD). Fiftythree patients genetically diagnosed with DMD, IMD and BMD, subdivided according to sites of mutations along the DMD gene, underwent a neuropsychological assessment, evaluating their general cognitive abilities, verbal memory, attention and executive functions. Twenty patients with mutations, terminating in exon 44 or starting at exon 45 were tested by polymerase chain reaction (PCR) amplification of microsatellites STR44, SK12, SK21 and P20 DXS269, in order to evaluate the integrity of the Dp140 promoter region. According to our statistical results, there was not a significant difference in terms of general intelligence between the allelic forms of the disease, a higher frequency of mental retardation was observed in DMD patients. The patients with BMD had better results on tests, measuring long-term verbal learning memory and executive functions. We found that patients lacking Dp140 performed more poorly on all neuropsychological tests compared to those with preserved Dp140. Overall, our findings suggest that the loss of Dp140 is associated with a higher risk of intellectual impairment among patients with dystrophinopathies and highlights the possible role of this distal isoform in normal cognitive development.</abstract>

Clinic of Neurology, University Hospital “Alexandrovska”, 1 Georgi Sofiiski str., Sofia 1431, Bulgaria

Clinic of Neurology, University Hospital “Alexandrovska,” Sofia, Bulgaria

Genetic Medico-Diagnostic Laboratory “Genica,” Sofia, Bulgaria

Department of Medical Chemistry and Biochemistry, Sofia Medical University, Sofia, Bulgaria

National Genetics Laboratory, Molecular Medicine Center, Sofia Medical University, Sofia, Bulgaria

Clinic of Child Neurology, University Hospital of Neurology and Psychiatry Sv. Naum, Sofia, Bulgaria

Department of Cognitive Science and Psychology, New Bulgarian University, Sofia, Bulgaria

Association Between Loss of Dp140 and Cognitive Impairment in Duchenne and Becker Dystrophies

<abstract><title style='display:none'>Abstract</title>Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (<italic>MBD2</italic>) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed <italic>MBD2</italic> mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of &lt;5 years and (iv) of &gt;5 years. The <italic>MBD2</italic> expression levels were 10.4-times increased on average in T2DM patients compared to controls. Consistent increase in DNA methylation fraction with the increase in T2DM duration was observed in <italic>Prdx2</italic> and <italic>SCARA3</italic> genes, connected to oxidative stress protection and in <italic>BRCA1</italic> and <italic>Tp53</italic> tumor-suppressor genes. In conclusion, increased <italic>MBD2</italic> expression in patients indicated general dysregulation of DNA methylation in T2DM. The elevated methylation of <italic>Prdx2</italic> and <italic>SCARA3</italic> genes suggests disturbance in oxidative stress protection in T2DM. The increased methylation of <italic>BRCA1</italic> and <italic>Tp53</italic> genes unraveled an epigenetic cause for T2DM related increase in cancer risk.</abstract>

Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia,

University Specialized Hospital for Active Treatment of Endocrinology ‘Acad. Ivan Penchev,’ Sofia,

Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia,

Department of Surgery, Medical Faculty, Medical University of Sofia, Sofia,

Department of Pathophysiology, Medical Faculty, Medical University of Sofia, Sofia,

Department of Pharmacology and Toxicology, Medical Faculty, Medical University of Sofia, Sofia,

Clinical Laboratory, University Hospital ‘Aleksandrovska,’Sofia,

Epigenetic alterations in patients with type 2 diabetes mellitus

<abstract><title style='display:none'>Abstract</title> Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy during childhood. Mutations in dystrophin (DMD) gene are also recognized as a cause of cognitive impairment. We aimed to determine the association between intelligence level and mutation location in DMD genes in Serbian patients with DMD. Forty-one male patients with DMD, aged 3 to 16 years, were recruited at the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade, Serbia. All patients had defined DMD gene deletions or duplications [multiplex ligation- dependent probe amplification (MLPA), polymerase chain reaction (PCR)] and cognitive status assessment (Wechsler Intelligence Scale for Children, Brunet-Lezine scale, Vineland-Doll scale). In 37 patients with an estimated full scale intelligence quotient (FSIQ), six (16.22%) had borderline intelligence (70&lt;FSIQ ≤85), while seven (18.92%) were intellectually impaired (FSIQ &lt;70). The FSIQ was not associated with proximal and distal mutations when boundaries were set at exons 30 and 45. However, FSIQ was statistically significantly associated with mutation location when we assumed their functional consequence on dystrophin isoforms and when mutations in the 5’-untranslated region (5’UTR) of Dp140 (exons 45-50) were assigned to affect only Dp427 and Dp260. Mutations affecting Dp140 and Dp71/Dp40 have been associated with more frequent and more severe cognitive impairment. Finally, the same classification of mutations explained the greater proportion of FSIQ variability associated with cumulative loss of dystrophin isoforms. In conclusion, cumulative loss of dystrophin isoforms increases the risk of intellectual impairment in DMD and characterizing the genotype can define necessity of early cognitive interventions in DMD patients.</abstract>

Clinic for Neurology and Psychiatry for Children and Youth, Dr. Subotica 6A, 11000 Belgrade, Serbia. Tel: +381-11-265-8355. Fax: +381-11-264-5064

Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia

Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia

Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

Intellectual Ability in the Duchenne Muscular Dystrophy and Dystrophin Gene Mutation Location

<abstract><title style='display:none'>Abstract</title>Our aim was to investigate the effects of antivascular endothelial growth factor (anti-VEGF) antibody Bevacizumab on endometrial explants and on apoptotic gene expression levels in the rat endometriosis model. Endometriotic implants were surgically formed, and rats treated with (i) 1 mg/kg single subcutaneous injection of depot leuprolide acetate; (ii) 2.5 mg/kg of single intaperitoneal injection of bevacizumab; (iii) intraperitoneal injection of saline. Histopathologic scores and adhesion scores of endometriotic foci and levels of Bcl-2-associated X protein (Bax), Cytochrome c (Cyt-c), B-cell lymphoma/ leukemia 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) mRNA gene expressions of endometriotic foci. Bevacizumab treatment decreased the endometriotic explant size compared with control. Bevacizumab-treated rats had lower total adhesion scores when compared with the control group. Semiquantitative evaluation of the persistence of endometrial epithelial cells in the explants showed a lower score in gonadotropin-releasing hormone (GnRH) agonist-treated rats compared with control rats. In Bevacizumab increased expression of Bax 3.1-fold, Cyt-c 1.3-fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold compared with the control group. The GnRH agonist increased expression of Bax 3.0 fold, Cyt-c 1.3 fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold, compared with the control group. This study suggests that a novel angiogenesis inhibitor, anti-VEGF antibody bevacizumab is as effective as GnRH agonist in the regression of the endometriotic lesions in rat endometriosis model. One possible mechanism of this effect is the induction of apoptosis.</abstract>

Dokuz Eylül University, Obstetrics and Gynecology, 35340, İzmir, Turkey

Sefa Kızıldağ, Ph.D., Dokuz Eylül University, Faculty of Medicine, 35340 İnciralti, İzmir, Turkey. Tel.: +90-2324124613. Fax: +90-2322590541

Menemen State Hospital, Obstetrics and Gynecology, 35660, İzmir, Turkey

Dokuz Eylül University, Pathology, 35340, İzmir, Turkey

A Novel Angiogenesis Inhibitor Bevacizumab Induces Apoptosis in the Rat Endometriosis Model

<abstract>
<title style='display:none'>Abstract</title>
Cardiovascular disease (CVD) risk factors, and particularly decreased high density lipoprotein cholesterol (HDL-C) dyslipidemia are prevalent in Assam, India. This study was undertaken to investigate whether <italic>Apolipoprotein A</italic>-<italic>I</italic> (<italic>APOA1</italic>) gene polymorphisms (G-75A and C+83T) were associated with <italic>i</italic>) the risk for decreased HDL-C, and <italic>ii</italic>) other CVD risk factors, <italic>viz</italic>. serum lipids, atherogenic indices, obesity, and blood pressure (BP). A total of 649 subjects were screened, from which 200 eligible individuals, classified as case group with decreased HDL-C levels (100 subjects) and control group with normal HDL-C levels (100 subjects) were enrolled and genotyped using polymersase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Lipid fractions [HDL-C, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG)] and atherogenic indices [Castelli’s Risk Indices-I and -II (CRI-I and -II), non-HDL-C fraction, atherogenic index of plasma (AIP), atherogenic coefficient (AC)] were estimated. The G-75A and C+83T loci were not associated with decreased HDL-C risk. This was confirmed across different genetic models (dominant, recessive, additive and allelic). Association was also absent with BP and obesity. However, the G-75A locus was associated with LDL-C, whereas the C+83T locus was associated with TG and VLDL-C. Furthermore, these sites had effects on atherogenic indices. The rare A allele at the G-75A locus was associated with adverse CRI-I, CRI-II, non-HDL-C and AC values, while the major C allele at the C+83T locus was associated with adverse AIP values. Thus, the pro-atherogenic G-75A polymorphism and the anti-atherogenic C+83T polymorphism represent important genetic loci that modulate CVD risk factors in subjects from Assam.
</abstract>

Association of the <italic>Apolipoprotein A</italic>-<italic>I</italic> gene polymorphisms with cardiovascular disease risk factors and atherogenic indices in patients from assam, Northeast India

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