Sener Tasdemir

Differential expressions of cancer-associated genes and their regulatory miRNAs in colorectal carcinoma.

Colorectal cancer is one of the frequently seen malignancies in the world. To date, several oncogenes and tumor suppressor genes have been identified and linked to colorectal cancer pathogenesis. Although recent advances in the diagnosis and therapy of colorectal cancer are promising, identifying novel genetic contributors is still high priority. In the present study, expression profile of some cancer-related genes and their regulatory miRNA molecules were evaluated by using a high-throughput real-time PCR method. For the study, a total of 54 patients diagnosed with CRC and normal colon tissue samples of 42 healthy controls were included. For the expression analysis, total RNA was extracted from FFPE tissue samples and converted to cDNA. All expression analyses were assessed by using Fluidigm Microfluidic Dynamic Array chips for 96 samples and the reactions were held in Fluidigm BioMark™ HD System Real-Time PCR. As a result of the study, expression of the ADAMTS1, FHIT, RUNX1, RUNX3 and WWOX genes was shown to be significantly altered in CRC tissues in contrast to normal tissue samples. Moreover, miR-378a-3p, miR-155-5p, miR-193b-3p, miR-96-5p, miR-17-5p, miR-27a-3p, miR-133b, miR-203a, miR-205-5p, miR-34c-5p, miR-130a-3p, miR-301a-3p, miR-132-3p, miR-222-3p, miR-34a-5p, miR-21-5p, miR-29a-3p and miR-29b-3p were found to be significantly deregulated in CRC. Consequently, results of the current study strongly suggest the involvement of novel cancer-related genes and their regulatory miRNAs in CRC physiopathology.

Is there any relationship between decreased AgNOR protein synthesis and human hair loss

Argyrophilic nucleolar organizing region associated proteins (AgNORs) play roles in cell proliferation and a variety of diseases. We attempted to determine whether decreased NOR protein synthesis causes human hair loss. We studied 21 healthy males who suffered hair loss on the frontal/vertex portion of the head. Hair root cells from normal and hair loss sites were stained for AgNOR. One hundred nuclei per site were evaluated and the AgNOR number and NORa/TNa proportions of individual cells were determined using a computer program. The cells from normal sites had significantly higher AgNOR counts than those from hair loss sites. Also, the cells from the normal sites had significantly higher NORa/TNa than cells from the hair loss sites. In the normal sites, the cells demonstrated more NOR protein synthesis than cells in hair loss sites. Therefore, decreased NOR protein synthesis appears to be related to hair loss in humans.

Vici syndrome in siblings born to consanguineous parents

Vici syndrome (OMIM 242840) is a rare syndrome and since its initial description by Vici et al. [1988], only 29 cases have been reported. We describe two brothers from healthy consanguineous Turkish parents with psychomotor delay, congenital bilateral cataracts, high palate, long philtrum, micrognathia, fair hair, and skin. They both had general hypotonia and elevated muscle enzymes. Magnetic resonance imaging (MRI) of the brain confirmed agenesis of corpus callosum in both patients. Secundum type atrial septal defect (in Patient 1) and mild mitral, tricuspid, and pulmonary insufficiency (in Patient 2) were detected by echocardiographic examination. Immunological studies were normal, as were chromosome karyotype analyses (46, XY). Both children had bilateral cutaneous syndactyly between second and third toes and also bilateral sensorineural hearing loss. Patient 1 had poor feeding and regurgitation necessitating a feeding tube; mild laryngomalacia was subsequently detected by bronchoscopy. Mutation analysis in patient 2 showed a homozygous p.R2483* (c.7447C > T) mutation in EPG5 gene. We report a summary of the clinical findings in our patients and 29 cases from the literature.

Correlation with Platelet Parameters and Genetic Markers of Thrombophilia Panel (Factor II g.20210G>A, Factor V Leiden, MTHFR (C677T, A1298C), PAI-1, β-Fibrinogen, Factor XIIIA (V34L), Glycoprotein IIIa (L33P)) in Ischemic Strokes

An important type of arterial thrombosis, ischemic stroke is associated with increased mortality risk, severe disability and life quality impairment. In this study, we analyzed mean platelet volume, platelet count values and genetic thrombophilia markers of patients who have ischemic stroke history and searched the relationship with genetic predisposition of ischemic strokes and platelet parameters. A retrospective, clinical trial was performed by reviewing the ischemic stroke history (except cryptogenic events) of 599 patients and 100 controls. The results of the genetic thrombophilia panel were used to classify the study group and control group into low and high risk for thrombophilia groups. The high-risk group included patients homozygous/heterozygous for Factor II g.20210G>A or Factor V Leiden mutations with/without any other polymorphism. The low-risk group included patients heterozygous or homozygous for MTHFR (C677T, A1298C), PAI-1, β-fibrinogen, Factor XIIIA (V34L) and glycoprotein IIIa (L33P) polymorphisms or negative in terms of both mutations and polymorphisms. The results of study showed us that high-risk group mutations are important risk factors for ischemic stroke but low-risk group polymorphisms are not significant. According to platelet parameters, although there was a significant difference between MPV and PLT values of ischemic stroke and control group, thrombophilia mutations and polymorphisms have not a significant effect on MPV and PLT values in ischemic stroke patients.

Comparison of fine needle aspiration biopsy and paraffin embedded tissue sections for measuring AgNOR proteins

Abstract Paraffin embedded tissue sections and fine needle aspiration biopsy (FNAB) are important methods for diagnosis. We compared thyroid tissue obtained by FNAB to paraffin embedded sections to determine whether there were differences in detection of the amounts of argyrophilic nucleolar organizing region (AgNOR) proteins. Twenty-two patients with papillary thyroid carcinoma were included in the study. Slides were prepared with both FNAB tissue and 3 μm sections of paraffin embedded tissue, and stained for AgNOR. One hundred nuclei per individual were evaluated; total AgNOR number/nucleus (TAn/TNn) and total AgNOR area/nuclear area (TAa/TNa) of individual cells were determined. Mean TAn/TNn and TAa/TNa values were 4.800 ± 1.118 and 13.382 ± 2.612, respectively, for FNAB samples; corresponding values were 2.406 ± 0.649 and 8.49 ± 0.893, respectively, for paraffin embedded sections. The differences between FNAB materials and paraffin embedded tissue sections were significant for the mean TAn/TNn and TAa/TNa values. Significant differences in the amounts of AgNOR protein detected were found between FNAB and paraffin embedded tissue sections.

A novel insertion mutation identified in exon 10 of the MEFV gene associated with Familial Mediterranean Fever.

BackgroundFamilial Mediterranean Fever (FMF), characterized by recurrent fever and inflammation of serous membranes, is an autosomal recessive disease caused by mutations in the Mediterranean fever (MEFV) gene. Around 296 mutations have been reported to date.MethodsTwo two-generation Turkish families with a total of four members diagnosed with FMF clinically were screened with DNA sequencing performed on exon 2 and exon 10 of the MEFV genes. Then, complete exome sequencing analysis of MEFV gene was done for four patients in whom novel mutation was detected.ResultsA novel single base Guanine (G) insertion mutation in the coding region of MEFV gene, named c.2330dupG (p.Gln778Serfs*4 or Q778SfsX4) resulting in a mutated Pyrin/Marenostrin protein was identified.ConclusionsThis is the first report of a new mutation in exon 10 of the MEFV gene in two Turkish families. This novel pattern of insertion mutation may provide important information for further studies on FMF pathogenesis.

Holoprosencephaly: ZIC2 mutation in a case with panhypopituitarism.

Abstract Background: Holoprosencephaly (HPE), the most common malformation of the brain, results from failed or incomplete separation of the embryonic forebrain (prosencephalon). HPE occurs in approximately 1 in 250 embryos and in about 1 in 10,000 births. It is etiologically heterogeneous, and may be caused by cytogenetic anomalies and teratogenic influences; it occurs as part of a syndrome, or due to heterozygous mutations in 1 of over 10 HPE-associated genes. ZIC2 mutations are the second-most common cause of non-syndromic non-chromosomal HPE (after sonic hedgehog) and occur de novo in 74% of the affected probands. Objective: The objective of the study was to describe the first case of ZIC2-related HPE with both anterior and posterior pituitary insufficiencies. Case presentation: We report about a 2-year-8-month-old boy who was born as a second child in a non-consanguineous healthy Turkish family. He has the characteristic ZIC2 phenotype: bitemporal narrowing, upslanting palpebral fissures, large ears, short nose with anteverted nares and broad and deep philtrum. Magnetic resonance imaging revealed alobar HPE. During laboratory investigation, his blood sodium level was 158 mmol/L and the specific gravity of his urine was 1.002. Serum osmolarity was 336 mOsm/L and urine osmolality was 135 mOsm/kg. His FT4 was 0.8 ng/dL and TSH was 0.79 mLU/mL. Response to vasopressin confirmed the diagnosis of central diabetes insipidus and TRH-stimulating test supported the central hypothyroidism. A frameshift mutation (NM_007129.2:c1091_1092 del, p.Gln364Leufs*2) in the ZIC2 gene was detected. Conclusion: Pituitary insufficiency other than isolated diabetes insipidus is a rare finding of HPE, and occurs most frequently in patients with GLI2 mutations (the phenotype of which typically does not include frank neuroanatomic anomalies such as HPE); ours is the only described patient with a ZIC2 mutation and both anterior and posterior pituitary dysfunction.