Sarcolemmal deficiency of sarcoglycan complex in an 18-month-old Turkish boy with a large deletion in the beta sarcoglycan gene.

Limb-girdle muscular dystrophy type 2E (LGMD-2E) is caused by autosomal recessive defects in the beta sarcoglycan (SGCB) gene located on chromosome 4q12. In this case report, the clinical findings, histopathological features and molecular genetic data in a boy with ß sarcoglycanopathy are presented. An 18-month-old boy had a very high serum creatinine phosphokinase (CPK) level that was accidentally determined. The results of molecular analyses for the dystrophin gene was found to be normal. He underwent a muscle biopsy which showed dystrophic features. Immunohistochemistry showed that there was a total loss of sarcolemmal sarcoglycan complex. DNA analysis revealed a large homozygous deletion in the SCGB gene. During 4 years of follow-up, there was no evidence to predict a severe clinical course except the muscle enzyme elevation and myopathic electromyography (EMG) finding. The presented milder phenotype of LGMD-2E with a large deletion in the SGCB gene provided additional support for the clinical heterogeneity and pathogenic complexity of the disease.

Cell free fetal DNA in the plasma of pregnant women with preeclampsia.

OBJECTIVE: Insufficient cytotrophoblast invasion to the myometrium is associated with preeclampsia, especially with the early-onset preeclampsia (before 34 gestational weeks). Several investigations have marked changes in the concentration of cell free fetal DNA in the maternal circulation of women with preeclampsia. However, these studies were not performed for early or late preeclampsia subgroups individually. The present authors planned to determine the levels of the cell free both fetal and maternal DNA in the maternal circulation in early preeclampsia subgroup and compare it with normotensive control cohort. MATERIALS AND METHODS: A total of 16 women; eight of these with preeclampsia and eight normotensive control cohorts with singleton male pregnancy between 28 and 32 gestational weeks were included in the study. Real-time PCR analysis was performed for determining the circulating cell free DNA levels. RESULTS: Cell free fetal DNA concentrations were higher in early preeclamptic women than control subjects. The authors found no statistically significant difference in each levels of maternal and total DNA between hypertensive and normotensive groups. CONCLUSIONS: The present findings suggest that the levels of cell free fetal DNA in maternal circulation were higher in pregnancies which are complicated with early preeclampsia than normotensive controls.

Structural chromosomal abnormalities in patients with mental retardation and/or multiple congenital anomalies: a new series of 24 patients.

Chromosomal abnormalities are a major cause of mental retardation and/or multiple congenital anomalies (MCA/MR). Screening for these chromosomal imbalances has mainly been done by standard karyotyping. The objective of this study was to report standard chromosome analysis and FISH screening of a series of 24 patients with MCA/MR. Structural chromosomal abnormalities were detected in 24 alterations and included 5 deletions, 2 duplications, 6 unbalanced translocations, 3 inversions, 2 insertions, 3 derivative chromosomes, 2 marker chromosomes and 1 isochromosome. We confirm that a high percentage of MCA/MR cases hitherto considered idiopathic is caused by chromosomal imbalances. We conclude that patients with MCA/MR should be routinely karyotyped.

Hydrophilic antioxidant capacities and total phenol content of seasonal fruits of Bangladesh.

INTRODUCTION: Consumption of fruits and vegetables helps to scavenge free radicals owing to the presence of antioxidant nutrients and secondary metabolites, especially polyphenolic compounds. This may lead to a reduction in the risk of diet-related chronic diseases. The purpose of the study was to determine the antioxidant capacity (AC) and total phenolic content (TPC) of selected seasonal fruits of Bangladesh. METHODS: Hydrophilic extracts from edible portions of fifteen fruits available in the summer season were analysed. Total phenol content was determined spectrophotometrically according to the Folin-Ciocalteau method while antioxidant capacity was determined by 2, 2-diphenyl-1-1-picrylhydrazyl radical scavenging activity (DPPH-RSA). RESULTS: TPC ranged from 0.6 +/- 0.01 to 0.01 +/- 0 mg Gallic acid equivalent (GAE)/g of fresh weight (FW). Antioxidant capacity varied from 4.882 +/- 0 to 0.113 +/- 0.03 micromol Torolox equivalents (TE)/g of FW. Carissa carandas showed the highest AC (4.882 +/- 0 micromol TE/g), while the lowest (0.113 +/- 0.3 micromol TE/g) was seen in Baccaura ramiflora. A positive and significant correlation (R2 = 0.957) between antioxidant capacity and total phenolic content of the analysed samples was identified. A significant and positive correlation (p < 0.05) between AC and TPC was found in Manikara zapota, Artocarpus heterophyllus, Litchi chinensis and Articarpus lakoocha. CONCLUSION: The data indicates that some indigenous seasonal fruits of Bangladesh contain high polyphenols that may serve as a potential source of dietary antioxidants.

Association of methylenetetrahydrofolate reductase C677T-A1298C polymorphisms with risk for esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.

Incidence of the esophagus adenocarcinoma has been dramatically increasing in Western countries since the last decade. Gastroesophageal reflux disease and Barrett's esophagus are risk factors for adenocarcinoma. Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may clarify the causes and events involved in esophageal carcinogenesis. In this study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12, folate, and plasma homocystein levels in patients with esophageal adenocarcinoma (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n = 26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the EAC and BE groups was significantly higher compared with the control group (P < 0.001, P = 0.003, respectively). In all patient groups, serum folate levels were significantly lower than that of the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). There was no statistically significant association between folate levels and MTHFR gene polymorphisms. No differences were found in terms of MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR gene polymorphisms and folate deficiency are not predictors of early esophageal carcinoma. However, further studies using larger series of patients are needed to evaluate the effect of genetic polymorphisms in the folate metabolic pathway and to clarify the role of folate deficiency and folate metabolism in the development of esophagus adenocarcinoma.

A rare case of monosomy 18p: translocation between chromosomes 18 and 21.

A rare case of monosomy 18p with molecular cytogenetic characterization of 18;21 whole arm translocation is presented. An 8-year-old gril with mental deficiency and growth deficiency was the child of a 45-year-old healthy mother and 50-year-old nonconsanguineous father with unremarkable prenatal history. She had a round face, flat nasal bridge, micrognathia and hypotonia. Cytogenetic studies revealed de novo 45,XX,del(18)t(18;21) karyotype, which was confirmed by fluorescence in situ hybridization (FISH).

Disorders of sexual development: an overview of 18 years experience in the pediatric Endocrinology Department of Ankara University.

INTRODUCTION: Disorders of sexual development (DSD) occur when the appearance of the internal and/or external genitalia is at variance with normal development for either sex. We reviewed the characteristics of patients with DSD. PATIENTS: Two hundred and eight children aged from newborn to 19 years with DSD from 1990 to 2008. RESULTS: 46,XY DSD (52.4%) was more common than 46,XX DSD (34.6%) and gonadal differentiation disorders (12.99%). Thirty-six (33.02%) patients were diagnosed with androgen resistance syndrome, 41 (37.61%) had 5alpha-reductase deficiency, 23 (21.10%) had testosterone synthesis disorders. Congenital adrenal hyperplasia was the most frequent underlying cause of 46,XX DSD. CONCLUSION: There are many difficult aspects in the diagnosis and management of DSD. Gender assessment teams of endocrine centers need a multidisciplinary approach for the diagnosis, medical and surgical treatment, genetic counseling, and psychosocial support of these patients.

Effects of imatinib mesylate on renin-angiotensin system (RAS) activity during the clinical course of chronic myeloid leukaemia.

The renin-angiotensin system (RAS) is involved in cell growth, proliferation and differentiation in bone marrow in an autocrine-paracrine manner, and it modulates normal and neoplastic haematopoietic cell proliferation. This study aimed to assess expressions of the RAS components, renin, angiotensinogen and angiotensin-converting enzyme (ACE), during imatinib mesylate treatment of patients with chronic myeloid leukaemia (CML). Expressions of RAS components were studied in patients with CML at the time of diagnosis (n = 83) and at 3, 6 and 12 months after diagnosis (n = 35) by quantitative real-time polymerase chain reaction. De novo CML patients had increased ACE, angiotensinogen and renin mRNA levels and these expression levels decreased following administration of imatinib. The RAS activities were significantly different among Sokal risk groups of CML, highlighting the altered biological activity of RAS in neoplastic disorders. The results of this study confirm that haematopoietic RAS affects neoplastic cell production, which may be altered via administration of tyrosine kinase inhibitors such as imatinib mesylate.

Prenatal diagnosis of a de novo supernumerary marker chromosome originating from chromosome 16.

Prenatal diagnosis of a de novo supernumerary marker chromosome originating from chromosome 16: A 37 year old pregnant woman was referred for amniocentesis at 18 weeks of gestation due to advanced maternal age and abnormal serum biochemistry. A nonsatellited, monocentric marker chromosome was observed with a frequency of 57% in cultured amniocytes. Parental karyotypes were normal. The marker chromosome was found to be derived from chromosome 16 by FISH using CEP16 and WCP16 probes. Marker chromosomes were not painted with M-FISH probe mixture, indicating an exclusively heterochromatin nature. CGH analysis using genomic DNA isolated from uncultured amniocytes also supported the M-FISH results. Genetic counseling was given to parents and the family decided to continue the pregnancy to term. The baby was born at 36 weeks of gestation without any dysmorphic features. Follow-up at 7 months of age revealed no developmental abnormalities.

Identification of frequency and distribution of the nine most frequent mutations among patients with 21-hydroxylase deficiency in Turkey.

UNLABELLED: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders mainly due to defects in the steroid 21-hydroxylase (CYP21A2) gene. METHODS: To determine the mutational spectrum in the Turkish population, the CYP21A2 active gene was analyzed in 100 unrelated patients with the classical form of 21-hydroxylase deficiency using PCR and RFLP. RESULTS: Mutations were detected in 78 patients: 64 patients were homozygous for one mutation, seven patients were compound heterozygous with different mutations on each chromosome, two patients were homozygous for two different mutations, five patients were heterozygous, and 22 patients harbored none of the tested mutations. The most frequent mutation was IVS2-13A/C (28.5%), followed by large gene deletion (17%), Q318X (11.5%), I172N (4%), V281L (3.5%), R356W (3.5%), 8-bp (3%), complex alleles (2%), P30L (1%) and E6 cluster (1%). CONCLUSION: The distribution of mutation frequencies in our study was slightly different from those previously reported in Turkey and in other parts of the world.

Novel chromosomal translocations in multiple myeloma: t(13;16)(q14;q24) and t(1;15)(q10;q26).

Multiple myeloma (MM) is a malignant plasma cell disorder that involves multiple genetic abnormalities. Chimeric transcription factors, created by gene fusion as a result of chromosomal translocations, have been implicated in the pathogenesis of the disease. Here, we report the conventional cytogenetic analysis of a MM patient that showed a complex set of novel chromosomal rearrangements, including t(13;16)(q14;q24) and t(1;15)(q10;q26). This is probably the result of fusion of previously known genes, and would contribute to prognostic significance of the disease.

Telomerase activity could be used as a marker for neoplastic transformation in gastric adenocarcinoma: but it does not have a prognostic significance.

Telomerase activity is responsible for telomere maintenance and is believed to be crucial in most immortal cells and cancer cells; however, its clinicopathological significance in gastric cancer remains to be clarified. The aim of the present study was to assess whether malignant progression of gastric adenocarcinoma correlates with telomerase activity. We also investigated the correlation between telomerase activity and histopathological findings. We examined telomerase activity in tumor specimens and adjacent normal tissues from 43 patients with gastric adenocarcinoma. Telomerase activity was measured quantitatively by the TRAPEZE Gel Based Telomerase Detection Kit. Approximately 98% of the tumor tissues were telomerase positive, but telomerase activity was detected not only in tumor tissues but also in normal gastric mucosa. Although telomerase activity was found to be higher in tumor samples than normal tissue for each subject, we could not find a general cut-off level for telomerase activity in gastric adenocarcinoma. In addition, telomerase activity was not correlated with tumor invasion, lymph node involvement and histological stage. Our results support the idea that telomerase reactivation is a common event in gastric adenocarcinoma and it is not related to histopathological parameters. Since it is difficult to set a cut-off level for this type of cancer, we suggest that the prognostic utility of telomerase assay has not yet reached the clinic in terms of predicting outcome for patients with gastric adenocarcinoma. For the assessment of gastric carcinoma, telomerase activity should be evaluated in both tumor and normal tissues, because normal gastric mucosa samples show appreciable telomerase activity.

Telomerase activity could be used as a marker for neoplastic transformation in gastric adenocarcinoma: but it does not have a prognostic significance

Telomerase activity is responsible for telomere maintenance and is believed to be crucial in most immortal cells and cancer cells; however, its clinicopathological significance in gastric cancer remains to be clarified. The aim of the present study was to assess whether malignant progression of gastric adenocarcinoma correlates with telomerase activity. We also investigated the correlation between telomerase activity and histopathological findings. We examined telomerase activity in tumor specimens and adjacent normal tissues from 43 patients with gastric adenocarcinoma. Telomerase activity was measured quantitatively by the TRAPEZE Gel Based Telomerase Detection Kit. Approximately 98% of the tumor tissues were telomerase positive, but telomerase activity was detected not only in tumor tissues but also in normal gastric mucosa. Although telomerase activity was found to be higher in tumor samples than normal tissue for each subject, we could not find a general cut-off level for telomerase activity in gastric adenocarcinoma. In addition, telomerase activity was not correlated with tumor invasion, lymph node involvement and histological stage. Our results support the idea that telomerase reactivation is a common event in gastric adenocarcinoma and it is not related to histopathological parameters. Since it is difficult to set a cut-off level for this type of cancer, we suggest that the prognostic utility of telomerase assay has not yet reached the clinic in terms of predicting outcome for patients with gastric adenocarcinoma. For the assessment of gastric carcinoma, telomerase activity should be evaluated in both tumor and normal tissues, because normal gastric mucosa samples show appreciable telomerase activity.

A novel Fryns "Anophthalmia-plus" syndrome associated with primary hypothyroidism.

A novel Fryns "anophthalmla-plus" syndrome associated with primary hypothyroidism: Here, we report a newborn male with "anophthalmia-plus" syndrome and primary congenital hypothyroidism. To our knowledge this is the first case of 'anophthalmia-plus' syndrome associated with congenital hypothyroidism in the literature up to date.

Toxic hepatitis in a case of Angelman syndrome associated with Lennox-Gastaut syndrome.

We report a 26-month-old boy with Angelman syndrome associated with Lennox-Gastaut syndrome, who developed a rash and a persistent toxic hepatitis after lamotrigine was added to valproate therapy. The patient had typical findings of both Angelman and Lennox-Gastaut syndromes. Chromosome analysis performing by FISH analysis showed a deletion in chromosome 15 (q11.2 q11.2). Although some cases of Angelman syndrome associated with Lennox-Gastaut syndrome were reported in the literature, valproate and/or lamotrigine induced toxic hepatitis in Angelman syndrome has hitherto never been described. We conclude that VPA and LTG combination should be given with great caution or avoided in patients with Angelman syndrome.

Gonadal dysgenesis and the Mayer-Rokitansky-Kuster-Hauser syndrome in a girl with 46,X,del(X)(pter-->q22:).

The association of mullerien duct with gonadal dysgenesis is extremely rare. We report such a case in a 19 year-old white woman with a 46,X,del(X)(pter-->q22:) karyotype.

Mental retardation with rare fragile site expressed at 2q11.

Several rare autosomal folate sensitive fragile sites were reported in individuals with mental retardation, neurological abnormalities, and multiple congenital malformations. Only three of them: fra(11)(q22.3), fra(X)(q27.3) and fra(X)(q28), are known to be associated with mental retardation and phenotypic abnormalities. A possible association of the other rare fragile sites with idiopathic mental retardation is still being discussed. Here, a girl who has a fragile site at 2q11 with minor congenital anomalies and mental retardation is presented. This case has recalled the question of idiopathic mental retardation that might be the clinical expression of rare FSFS. Fragility was observed at 2q11 with a frequency of 3% in her cells along with a partial endoreduplication at 2 q11-->qter.

Effects of factor V gene G1691A, methylenetetrahydrofolate reductase gene C677T, and prothombin gene G20210A mutations on deep venous thrombogenesis in Behçet's disease.

OBJECTIVE: Behçet's disease (BD) is a multisystemic disease of unknown etiology, characterized by aphthous ulcerations and uveitis, that is common in the Turkish population. Venous involvement is observed in 25% of the cases. While superficial thrombophlebitis is the most common finding, deep venous thrombosis (DVT) follows it. Hyperactivity in the coagulation pathway, hypoactive anticoagulation mechanisms, or faulty fibrinolysis generate a tendency for thrombogenesis. Mutations of the genes involved in these pathways may cause predisposition to thrombosis. METHODS: Possible roles of methylenetetrahydrofolate reductase (MTHFR) gene C677T, factor V (FV) gene G1691A (Leiden), and prothrombin gene G20210A polymorphisms in venous thrombogenesis were evaluated in patients with BD; 100 healthy people, 30 BD patients without DVT, 30 BD patients with DVT, and 30 patients with idiopathic DVT were studied with the restriction fragment length polymorphism method for these 3 polymorphisms. The frequencies of these mutations for each group, separately and in combinations, are described. RESULTS: Among the 3 mutations, FV Leiden mutation was found to be a risk factor for DVT. An association between FV Leiden mutation and BD was likely, but FV Leiden mutation did not increase the risk for deep venous thrombogenesis in BD patients. MTHFR gene C677T mutation does not increase risk of DVT in BD either alone or combined with FV Leiden mutation. CONCLUSION: Although a thrombotic tendency is one of the major characteristics of BD, we found no association between these 3 thrombogenetic mutations and BD patients with thromboses.

Molecular alterations in the TP53 gene of peripheral blood cells of patients with chronic myeloid leukemia.

The TP53 gene has been extensively studied in patients with chronic myeloid leukemia (CML), both in chronic phase and in blast crisis. Mutations in the gene were found in up to 30% of the patients, especially among those in blast crisis. We report the results of an analysis of 29 blood samples from CML patients: 8 samples from chronic phase patients, 8 from patients in the accelerated phase, and 13 from patients in blast crisis. By using genomic DNA, we sequenced PCR products of the coding exons and most introns of the TP53 gene, finding genetic changes in 30% of the blast crisis samples and 12% in chronic phase. All mutations were found in introns and were previously unreported. Immunocytochemical studies revealed accumulation of TP53 in blood cells of samples both from chronic phase and blast crisis patients. Since these samples had no TP53 mutations, we believe that wild type TP53 accumulates in blood cells of CML patients. Our results, therefore, indicate that molecular changes in coding regions of the TP53 gene are rare. The significance of the abundance of intronic changes should be investigated further. Accumulation of wild type TP53 in CML cells may indicate an additional mechanism involving this gene in the pathogenesis of this disease.