Evaluation of chromosomal abnormalities in the postnatal cohort: A single-center study on 14,242 patients.

BACKGROUND AND AIM: Chromosomal analysis is a laboratory technique used to examine the chromosomes of an individual, offering insights into chromosome numbers, structures, and arrangements to diagnose and comprehend genetic diseases. This retrospective study provides a comprehensive understanding of the distribution by indications in a large cohort of 14,242 patients and the frequency of chromosomal abnormalities in different clinical populations. METHOD: The study examined various indications for karyotype evaluation, with recurrent pregnancy loss being the most common indication, followed by intellectual disability, dysmorphic features, congenital anomalies, and developmental delay. RESULTS: The overall chromosomal abnormality rate was found to be 5.4%, with numerical abnormalities accounting for the majority of cases (61.7%). Trisomies, particularly trisomy 21, were the most frequent numerical abnormalities. In terms of structural abnormalities, inversions and translocations were the most commonly identified. The rates of chromosomal anomalies varied in specific indications such as amenorrhea, disorders of sex development, and Turner syndrome. The study also highlighted significant differences between males and females in the presence of chromosomal abnormalities across certain indications. Males exhibited a higher incidence of chromosomal abnormalities in cases of Down syndrome and infertility, whereas females showed higher abnormalities in terms of recurrent pregnancy loss. CONCLUSION: While this study provides valuable insights into the frequency and distribution of chromosomal abnormalities, it has limitations, including its retrospective design and reliance on data from a single medical genetics department. Nevertheless, the findings emphasize the importance of karyotype analysis in diagnosing chromosomal disorders and providing appropriate management, while also pointing to potential gender-related variations in chromosomal abnormalities that warrant further investigation.

Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing.

The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.

EVs vs. EVs: MSCs and Tregs as a source of invisible possibilities.

Extracellular vesicles (EVs) are produced by various cells and exist in most biological fluids. They play an important role in cell-cell signaling, immune response, and tumor metastasis, and also have theranostic potential. They deliver many functional biomolecules, including DNA, microRNAs (miRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA), lipids, and proteins, thus affecting different physiological processes in target cells. Decreased immunogenicity compared to liposomes or viral vectors and the ability to cross through physiological barriers such as the blood-brain barrier make them an attractive and innovative option as diagnostic biomarkers and therapeutic carriers. Here, we highlighted two types of cells that can produce functional EVs, namely, mesenchymal stem/stromal cells (MSCs) and regulatory T cells (Tregs), discussing MSC/Treg-derived EV-based therapies for some specific diseases including acute respiratory distress syndrome (ARDS), autoimmune diseases, and cancer.

An overview of the genetic aspects of hair loss and its connection with nutrition.

Hair loss is a widespread concern in dermatology clinics, affecting both men's and women's quality of life. Hair loss can have many different causes, which are critical to identify in order to provide appropriate treatment. Hair loss can happen due to many variables, such as genetic factors or predisposition, vitamin and mineral deficiencies, skin problems, hair growth disorders, poor diet, hormonal problems, certain internal diseases, drug use, stress and depression, cosmetic factors, childbirth, and the chemotherapy process. Treatment for hair loss varies depending on the type of alopecia, deficiency, or excess of structures such as vitamins and minerals, and also on hair and skin structure. The Mediterranean diet is characterized by low amounts of saturated fat, animal protein, and high amounts of unsaturated fat, fiber, polyphenols, and antioxidants. The main nutrients found in the Mediterranean Diet are rich in antioxidant, anti-inflammatory components. It also has an important place in hair loss treatment, since recently treatment strategies have included polyphenols and unsaturated oils more and more frequently. The goal of this work was to review published articles examining alopecia and its types, the many micronutrients that affect alopecia, and the role of the Mediterranean diet in alopecia. The literature shows that little is known about hair loss, nutritional factors, and diet, and that the data collected are conflicting. Given these differences, research into the function of diet and nutrition in the treatment of baldness is a dynamic and growing topic.

Implication of the Mediterranean diet on the human epigenome.

Epigenetics, defined as "hereditary changes in gene expression that occur without any change in the DNA sequence", consists of various epigenetic marks, including DNA methylation, histone modifications, and non-coding RNAs. The epigenome, which has a dynamic structure in response to intracellular and extracellular stimuli, has a key role in the control of gene activity, since it is located at the intersection of cellular information encoded in the genome and molecular/chemical information of extracellular origin. The focus shift of studies to epigenetic reprogramming has led to the formation and progressive importance of a concept called "nutriepigenetics", whose aim is to prevent diseases by intervening on nutrition style. Among the diet types adopted in the world, the renowned Mediterranean Diet (MD), being rich in unsaturated fatty acids and containing high levels of whole grain foods and large quantities of fruits, vegetables, and legumes, has shown numerous advantages in excluding chronic diseases. Additionally, the fact that this diet is rich in polyphenols with high antioxidant and anti-inflammatory properties has an undeniable effect in turning some cellular pathways against the disease. It is also apparent that the effects of polyphenols on the epigenome cause changes in mechanisms such as DNA methylation and histone acetylation/deacetylation, which have a regulatory effect on gene regulation. This review presents the effects of long-term consumption of nutrients from the MD on the epigenome and discusses the benefits of this diet in the treatment and even prevention of chronic diseases.

Evaluation of Utilizing the Distinct Genes as Predictive Biomarkers in Late-Onset Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by a devastating decline in cognitive activities among all types of dementia, and it severely affects the quality of life. Late-onset AD (LOAD) occurs after the age of 65 years and develops sporadically. Although aging comes first along the main risk factors underlying LOAD, disease-causing susceptibility genes have been associated with disease pathogenesis. In our study, we included the genes PARP1 , POLB , HTRA2 , SLC1A2 , HS1BP3 , and DRD3 to be investigated in LOAD patients based on their expression levels. Within this framework, we aimed to determine the possible functions of these genes in the pathophysiology of the disease. We investigated whether the utilization of these genes as biomarkers in the early diagnosis of LOAD may help the treatment scheme to be applied in the clinic. We involved 50 individuals in the study and collected peripheral blood samples from the patients and control groups for molecular genetic analysis. Subsequently, RNA was extracted from the peripheral blood samples, and expression analyzes were performed using qualitative reverse transcription polymerase chain reaction. The results obtained were evaluated by using proper statistical methods. Our results demonstrated that there was no difference between patient and control groups in terms of HTRA2 , DRD3 , HS1BP3 , and POLB genes. The expression levels of the SLC1A2 and PARP1 genes were significantly lower in the patient group compared with the control group. In conclusion, we presume that the PARP1 and SLC1A2 genes can be utilized as molecular biomarkers for LOAD.

SAHA induce hippo pathway in CCA cells without increasing cell proliferation.

BACKGROUND: Cholangiocarcinoma is a malignant tumor originating from bile duct epithelial cells. Since tumor metastasis is associated with poor prognosis and short-term survival of patients, there is an urgent need for alternative therapeutic approaches for CCA. Because of that reason, we aimed to investigate effect of SAHA which is known as HDAC inhibitor on extrahepatic cholangiocarcinoma cell line (TFK-1). METHODS: Cell cycle was measured by Muse Cell Analyzer. YAP, TAZ, TGF-ß protein levels were determined by western-blotting method. TEAD (1-3), TIMP2 and TIMP3 genes level were determined by real-time PCR analysis. RESULTS: We have seen the positive effects of SAHA on the TFK-1 cell line as it reduces cell viability and arresting cells in the G0/G1 phase. We also observed the negative effects of SAHA, as it increases the expression levels of YAP, TAZ, TGF-ß protein and TEAD (1-3) gene. We also found that SAHA reduced the expression levels of TIMP2 and TIMP3 in TFK-1 cells, but was not statistically significant. CONCLUSIONS: Although observing its antiproliferative effects, these negative effects may be related to the cells being resistant to the drug or the remaining cells having a more aggressive phenotype. Therefore, we think that caution should be exercised in the use of this drug for CCA treatment.

Detection of mutations in CML patients resistant to tyrosine kinase inhibitor: imatinib mesylate therapy.

Imatinib mesylate, a tyrosine kinase inhibitor, is the first choice in chronic myeloid leukemia treatment. However, resistance to imatinib may develop with time and in some cases, patients may not respond at all to imatinib. Progressive resistance to imatinib therapy is often due to mutations in the BCR/ABL region. Within the scope of our study 124 patients were evaluated via pyrosequencing between 2015 and 2020. In this regard, 32 patients who have a partial response and have no response to imatinib therapy were included in the study. In addition, next-generation sequencing (NGS) analysis was performed on 15 patients who were resistant to imatinib treatment according to the molecular follow-up reports. With pyrosequencing, 5 cases out of a total of 124 were found to be positive. This means that approximately 4.03% of the proportion is positive. But when we examined only 32 patients who have a partial response and have no response to imatinib therapy this rate is rising 15.6%. NGS analysis was performed with 15 patients who have no mutation with pyrosequencing of 32 patients and VUS (Variant of Uncertain Significance) mutation was detected in one. In this study, our aim was to determine the mutations of the BCR/ABL and to evaluate the mutations by NGS and pyrosequencing. Our study is important in terms of comparing the pyrosequencing with NGS mutation rates, drawing attention to the clinical importance of log reduction.

The Effect of EZH2 Inhibition through DZNep on Epithelial-Mesenchymal Transition Mechanism.

Although the molecular pathogenesis of hepatocellular carcinoma (HCC) is uncertain, it is known that the epithelial-mesenchymal transition (EMT) mechanism and epigenetic changes have an important role. This study was focused on evaluating the relationship of 3-Deazaneplanocin A (DZNep) with the EMT mechanism, which is a histone methyltransferase inhibitor on HCC and is also known as an enhancer of zeste homolog 2 (EZH2) inhibitor. Cell viability of HepG2 cells (HCC cell line) assessed for DZNep over 72 hours with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, colony-forming assay, apoptosis assay, RNA isolation, cDNA synthesis, and real-time PCR (RT-PCR) were performed to see the effect of DZNep on HepG2 cells. DZNep reduced cell proliferation for 72 hours, also significantly reduced colony formation in addition it increased the total apoptosis. DZNep on EZH2, E-cadherin, N-cadherin, and Vimentin (Vim) gene expressions was given different results by either decreasing or increasing the expressions. In this study, we observed a positive effect of DZNep on apoptosis and TIMP3 expression level and decreased colony formation. However, it gave complicated results with the level of gene expression E-cadherin and TIMP2, increase the level of Vim and MMP2 expression. Therefore, we think that further studies are necessary to clarify the role of DZNep.

Suberoylanilide Hydroxamic Acid (SAHA) Reduces Fibrosis Markers and Deactivates Human Stellate Cells via the Epithelial-Mesenchymal Transition (EMT).

Hepatic fibrosis is known as the accumulation of connective tissue secondary to chronic damage to the liver. Epithelial-mesenchymal transition (EMT) corresponding increase in liver fibrogenesis was shown with immunohistochemistry and PCR-based studies. Suberoylanilide hydroxamic acid (SAHA), a synthetic compound approved as a histone deacetylase inhibitor (HDAC) by the FDA to treat cutaneous T-cell lymphoma is under investigation for the treatment of lung and renal fibrosis. Experimental modeling for hepatic fibrosis can be constructed with an LX2 cell line isolated from human hepatic stellate cells (HSCs). In this study, we aimed to investigate the modulation of SAHA in the pathogenesis of liver fibrosis by detecting the levels of proteins; (E-cadherin (E-cad), N-cadherin (N-cad), Vimentin (Vim), and genes; E-cad, N-cad, Vim, transforming growth factor-beta (TGF-ß), alpha-smooth muscle actin (α-SMA), type 1 collagen (COL1A1), type 3 collagen (COL3A1)) that play a significant role in EMT with the LX2 cell line. We also evaluated the action of SAHA with cell proliferation, clonogenic, and migration assay. Cell proliferation was performed by flow cytometry. All the protein levels were determined by Western blot analysis, and gene expression levels were measured by Real-Time PCR. Our study observed that SAHA treatment decreased cell viability, colony formation and migration in LX2 cells. We found that SAHA increased E-cad expression level, while it decreased N-cad, Vim, COL1A1, COL3A1, α-SMA TGF-ß genes expression levels. SAHA decreased the level of E-cad, N-cad, and Vim protein levels. We thought that SAHA possesses potent antifibrotic and anti-EMT properties in LX2.

Comparing expression levels of PERIOD genes PER1, PER2 and PER3 in chronic insomnia patients and medical staff working in the night shift.

AIM: This study was done to determine the changes in expression levels of PERIOD family genes in chronic insomnia patients and night shift healthcare staff with irregular sleep hours. METHOD: A total of 24 chronic insomnia patients aged between 25 and 55 that were admitted to Erciyes University Medical Faculty Neurology Polyclinic, 32 medical staff aged between 23 and 42 that work in night shifts with no neurological diagnosis were included as volunteers in the experiment. Additionally, a control group consisting of 29 healthy individuals between 21 and 50 years of age who do not work in shifts was volunteered in the study. Since PERIOD family gene expressions are affected by time of day and season changes, blood samples were taken from the groups within the same week and at the same time periods. RNA isolation followed by cDNA synthesis from leukocytes was performed from blood samples that were kept in 10 cc EDTA tubes. Expression levels of the genes were then determined by quantitative PCR method and analysed. RESULTS: There was a significant decrease in the expression levels of PER1 and PER2 genes in chronic insomnia and night shift healthcare professional groups compared to the control group (p = 0.0001 for PER1; p = 0.0023 for PER2), but no significant change was observed in PER3 gene (p = 0.619). DISCUSSION: The decrease in PER1 and PER2 gene expressions in chronic insomnia and shift working healthcare personnel seems to be more of a result for short sleep periods than a cause.

Increased EGFR mRNA Expression Levels in Non-Small Cell Lung Cancer.

OBJECTIVE: In this study, we investigated the frequency of Epidermal growth factor receptor (EGFR) gene mutations, the level of EGFR mRNA and protein expressions in Turkish population for indicating substantial differences in the frequency of EGFR mutations, EGFR amplification and EGFR protein expression between populations and the effect of these parameters in response to EGFR tyrosine kinase inhibitors. MATERIALS AND METHODS: The study included 34 patients with non-small cell lung cancers. The RNA and DNA were extracted from the normal and tumor side of the lung tissue removed by surgery. To investigate the most common mutations in the EGFR gene, exon 19 was sequenced and mutation specific PCR was performed for detecting the L858R mutation in exon 21. EGFR mRNA expression was measured by relative quantitative reverse transcription PCR. The EGFR protein levels were detected with immunohistochemistry methods from the sections of the patients' paraffin blocks. RESULTS: No EGFR mutation in exon 19 or L858R mutation in exon 21 were detected in the patients. Overexpression of EGFR gene mRNA was identified in 16 of 34 (%47) patients and overexpression of EGFR protein was detected in 15 of 34 (%44) patients. Statistical analysis was not significant for the correlation between sex, age, smoking, histopathology, pathological stage and overexpression of EGFR mRNA and protein. CONCLUSION: It was found that in Turkish population, EGFR mutation in exon 19 and L858R mutation were very rare, EGFR protein expression was similar and EGFR mRNA expression significantly increased compared to the literature. Markedly increased EGFR mRNA expression ratios in the absence of activating mutations showed that identifying the EGFR mRNA expression level for prediction of response to EGFR tyrosine kinase inhibitors might be significant in the Turkish population.

The molecular basis and genotype-phenotype correlations of congenital adrenal hyperplasia (CAH) in Anatolian population.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder due to presence of mutations in the genes involved in the metabolism of steroid hormones in adrenal gland. There are two main forms of CAH, classic form and non-classic form. While classic form stands for the severe form, the non-classic form stands for the moderate and more frequent form of CAH. The enzyme deficiencies such as 21-hydroxylase, 11-beta-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase deficiencies are associated with CAH. In this study, we aimed to investigate CYP21A2, CYP11B1, HSD3B2 genes which are associated with 21-hydroxylase, 11-beta-hydroxylase and 3-beta-hydroxysteroid dehydrogenase enzyme deficiencies, respectively, in 365 individuals by using Sanger sequencing method. We emphasized the classification of variants according their disease causing potential, and evaluated variants' frequencies including newly discovered novel variants. As a result, 32 variants of CYP21A2 including 10 novel variants, 9 variants of CYP11B1 including 3 novel variants and 6 variants of HSD3B2 including 4 novel variants were identified. The conclusions of our study showed that in Anatolia, discovery of novel variants is quite common on account of tremendous ratios of consanguineous marriages which increases the frequency of CAH. These results will contribute to the understanding of molecular pathology of the disease.

Can the expression level of PIWIL 2 gene be a serum marker for prostate cancer? A single-center prospective study.

OBJECTIVE: The aim of the present study was to evaluate the predictive value of the serum expression level of Piwi-like 2 (PIWIL2), a stem cell protein, for prostate cancer (PCa). MATERIALS AND METHOD: This randomized and prospective study included a total of 60 volunteers between 50 and 75 years old. Cases were assigned to three groups according to prostate-specific antigen (PSA) elevations and pathology reports, with 20 participants in each group. The first group included patients with a PSA level of >4 ng/dL and with PCa, the second group included patients with a PSA level of >4 ng/dL and with benign prostate hyperplasia, and the third group included patients with a PSA level of ≤4 ng/dL and with benign prostate hyperplasia. The levels of serum PSA and PIWIL2 expressions were compared between the groups. RESULTS: The median serum PSA levels were 28.5 (4.6-98.1) ng/mL, 8.89 (4.3-24.1) ng/mL, and 2.4 (0.3-3.8) ng/mL for groups 1, 2, and 3, respectively. The PSA levels were significantly different between the groups (p<0.001). The median PIWIL2 gene expression levels were 2.54 (0.28-9.27), 2.27 (0.6-9.38), and 1.17 (0.26-3.07) for groups 1, 2, and 3, respectively. The PIWIL2 gene expression level was found to be lower in patients with a PSA level of <4 (p=0.02). No significant difference was observed between patients with and without cancer among those with a PSA level of ≥4 (p>0.05). Patients diagnosed with cancer were grouped according to the criteria of the International Society of Urological Pathology (ISUP), and PIWIL2 gene expression was observed to be significantly higher among patients with ISUP of >3 than among those with ISUP of ≤3 (p=0.04). CONCLUSION: In our study, it was observed that the serum level of PIWIL2 gene expression could not be a diagnostic indicator of PCa; however, it could be a beneficial prognostic indicator particularly for progressed disease.

The effects of streptozotocin-induced diabetes on ghrelin expression in rat testis: biochemical and immunohistochemical study.

INTRODUCTION: Ghrelin is a hormone which has effects on the secretion of growth hormone, gastrointestinal system, cardiovascular system, cell proliferation and reproductive system. The present study we focused on the relation between ghrelin and GHS-R1a gene expression and the regulation of their expression in the testes of diabetic rats. MATERIAL AND METHODS: 40 male Wistar albino rats were divided into four groups: control, and sampled 4, 8 and 12 weeks after induction of diabetes by streptozotocin (STZ) intraperitoneal injection (40 mg/kg). The rats were decapitated under ketamine anesthesia and their testes were removed. Blood was obtained from heart and serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were measured by ELISA. Tissue ghrelin and GHS-R mRNA levels were determined by qRT-PCR, while ghrelin protein expression was studied by immunohistochemistry. Histopathological damage scores were also assessed. RESULTS: Eight weeks after diabetes induction serum FSH level was increased, whereas LH and testosterone concentrations decreased. The ghrelin and GHS-R1a gene expression and ghrelin immunohistochemistry score first tended to increase after first four weeks of diabetes, and then tended to decrease. Ghrelin-immunopositive cells were detected in Leydig cells in all groups of rats, however, not in the germinal epithelium. Congestion of vessels and hemorrhage, formation of the vacuoles in spermatogonia and spermatocytes, desquamation of spermatids in the lumen and disorganization of seminiferous tubule germinal epithelium were observed in testis of all the diabetic rats. In addition, mean testicular biopsy score and mean seminiferous tubule diameter were getting lower in diabetic animals. CONCLUSION: Our results suggest that diabetes affects ghrelin expression in rat testis.

Does the level of WT1 expression predict the outcome in Philadelphia-negative myeloproliferative neoplasms?

AIMS: Despite the clinical importance of the leukemic transformation of chronic myeloproliferative neoplasms (MPNs), very little is known about markers that predict leukemic transformation. We studied WT1 expression in 37 MPN patients diagnosed as bcr-abl negative and JAK2 (V617F) positive with a molecular genetic test, and 23 healthy controls. RESULTS: WT1 expression is higher in MPN patients compared with normal controls (p=0.002). According to the WT1 expression levels, patients were divided into two groups: high (≥0.205) and low (0-0.205) WT1 expression. Two out of six patients with a high WT1 expression level transformed to myelodysplastic syndrome at a 42- and 46-month follow-up, respectively. CONCLUSIONS: Our results suggest that the overexpression of WT1 may play an important role in the leukemic transformation of MPNs.

Erythropoietin improves brain development in short-term hypoxia in rat embryo cultures.

BACKGROUND: Hypoxic ischemic encephalopathy continues to be a significant cause of death and disability worldwide. Erythropoietin (EPO) has the potential to lessen neurologic sequelae due to hypoxia-ischemia. METHODS: The in vitro effects of EPO on total embryonic development and brain VEGF receptor (VEGFR) expressions were investigated in 50 rat embryos at 9.5 days of gestation that were cultured in whole rat serum (WRS). According to the study protocol, the embryos were divided into two groups. The first group is comprised hypoxia, 100 and 50 U/ml EPO after hypoxia groups. Group 2 comprised control (WRS) and WRS+EPO. After 48-h culture, the embryos from each group were harvested to be analyzed according to a morphological scoring system and also genetically to measure brain VEGFR expression. RESULTS: The mean morphological scores for the embryos grown in control, WRS+EPO, hypoxia, and in the presence of 100 and 50 U/ml EPO in hypoxic medium were 55.30±7.22, 52.10±5.27, 23.0±4.60, 36.20±5.07, and 19.70±5.07, respectively. Expressions of VEGFR-1, -2, -3 were significantly elevated in the 100U/ml EPO and WRS+EPO groups compared to the hypoxia group (p<0.05). CONCLUSIONS: These results support the conclusion that (1) VEGFR-1, -2, -3 may increase with EPO treatment in hypoxic conditions, (2) VEGF and EPO may be part of a self-regulated physiological protection mechanism to prevent neuronal injury including in utero neural tube defects.

Unbalanced 3;22 translocation with 22q11 and 3p deletion syndrome.

This report describes a 25-day-old Turkish boy with unbalanced 3;22 translocation that includes the 22q11.2 deletion and 3p25 deletion syndrome. The karyotype was 45, XY,der(3)t(3;22)(p25;q11),-22. Although no immunological dysfunction could be demonstrated, the boy presented some manifestations of DiGeorge anomaly (DGA), which has been associated with monosomy for the same region of chromosome 22, velocardiofacial syndrome (VCFS), and the 3p deletion syndrome. Clinical features include short stature, hypertelorism, low set ears, cleft lip with cleft palate, short neck, truncus arteriosus, micropenis, clubfoot, over riding toes on right foot, four digits on left foot and growth delay. In addition he had feeding difficulties, respiratory infections, and developmental delay. Fluorescence in situ hybridization (FISH) studies confirmed loss of the proximal DiGeorge chromosomal region (DGCR). Array CGH analysis showed the deletion sites on chromosomes 3 and 22. This report documents a rare chromosomal aberration that causes the 22q11 and 3p deletion syndrome simultaneously.

Expression of WT1 gene in multiple myeloma patients at diagnosis: is WT1 gene expression a useful marker in multiple myeloma?

Monitoring patients with multiple myeloma during and after treatment for the presence of residual myeloma cells (minimal residual disease - MRD) has been shown to give a major insight into the effectiveness of treatment. It has been reported that Wilms' tumor gene (WT1) expression levels measured by real-time quantitative polymerase chain reaction was useful as an indicator of minimal residual disease in leukemia and myelodysplastic syndrome. The aim of this study was to measure levels of WT1 expression, in order to find a possible association between the expression of this gene and multiple myeloma at diagnosis. If an association was found, the WT1 gene could be evaluated as an MRD marker by comparison with other prognostic factors. We investigated peripheral blood WT1 expression level measured by real-time light cycler quantitative polymerase chain reaction in 50 newly diagnosed multiple myeloma patients. The normal WT1 gene copy number was found to be <23/microl cDNA and all patients with myeloma were found to have normal WT1-mRNA levels. On this basis WT1 expression analyses is unlikely to be a useful genetic marker for routine clinical use in multiple myeloma patients at diagnosis.

GnRH-II mRNA expression in tumor tissue and peripheral blood mononuclear cells (PBMCs) in patients with malignant and benign ovarian tumors.

OBJECTIVE: To investigate the expression of the second form of GnRH (GnRH-II) in tumor tissue and peripheral blood mononuclear cells (PBMCs) in malignant and benign ovarian tumors in humans. STUDY DESIGN: Sixty-six women were studied: 24 with epithelial ovarian carcinomas, 22 with benign ovarian tumors and 20 in the control group undergoing surgery. Malignant, benign and normal ovarian tissue and PBMCs were obtained for measurement of GnRH-II mRNA levels using quantitative real-time RT-PCR. RESULT(S): The expression of GnRH-II was found to be 1.5 times higher in malignant ovarian tumors compared with benign ovarian tumors and the control group in post-menopausal patients (P<0.01). In the post-menopausal patient group with malignant ovarian tumors, there were significant positive correlations between serum FSH level and ovarian tissue GnRH-II mRNA expression (r=0.68; P=0.03), and serum LH level and ovarian tissue GnRH-II mRNA expression (r=0.71; P=0.02). Controls, benign and malignant groups were similar in terms of GnRH-II expression in PBMCs in the pre- and post-menopausal periods. There was no significant correlation between ovarian tissue GnRH-II mRNA expression vs. PBMC GnRH-II mRNA expression in patient and control groups. CONCLUSION(S): We have shown increased GnRH-II expression in human ovarian cancer tissue in post-menopausal women in vivo. Expression of GnRH-II in PBMCs did not reflect the local GnRH-II expression levels in ovarian tissue. These preliminary data suggest that local GnRH-II may participate in the regulation of ovarian tumor growth in post-menopausal women.