Publications by authors named "Sukru Palanduz"

52 Publications

Indication for Y Chromosome Microdeletion Analysis in Infertile Men: Is a New Sperm Concentration Threshold Needed?

Urology 2020 Dec 6;146:113-117. Epub 2020 Oct 6.

Istanbul University, Istanbul Faculty of Medicine, Urology Department, Istanbul, Turkey.

Objective: To describe the prevalence of Y-chromosome deletions in patients with a sperm concentration of less than 5 million/mL. To also determine a new sperm threshold for Y-chromosome analysis in men with infertility.

Methods: A total of 3023 patients who had a semen concentration of less than 5 million/mL included in this retrospective study. All of these patients had a genetic evaluation, hormonal evaluation, and 2 abnormal semen analyses.

Results: Y-chromosome deletions were present in 116 (3.8 %) patients with sperm concentration <5 million/mL. The frequency of a Y-chromosome deletions was 6.8%, 1.0%, 0.15% in azoospermic men, in men with sperm concentrations of 0-1 million /mL, in men with sperm concentrations of 1-5 million/mL. Patients were divided into 2 groups regarding the determined new sperm threshold. The sensitivity and specificity of the Y-chromosome deletions test were 92.2.7% and 49.3 %, 99.1%, and 22.1% in patients with azoospermia and sperm concentrations <1 million/mL, respectively. If the sperm concentration thresholds of azoospermia or <1 million/mL, are applied, the number of tests decreased to 50.5% (1442 tests) and 23.1% (643 tests), respectively. Approximately $108,150 and $48,225 would be saved if the sperm thresholds were azoospermia and <1 million/mL, respectively CONCLUSION: The current threshold of sperm concentration for Y-chromosome deletions is controversial. The new proposed sperm threshold for genetic testing of 1 million/mL would increase sensitivity and more cost-effective compared to the current threshold.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2020.09.032DOI Listing
December 2020

DNA damage effects of inhalation anesthetics in human bronchoalveolar cells.

Medicine (Baltimore) 2019 Aug;98(32):e16518

University of Health Science, Sisli Hamidiye Etfal Research and Training Hospital, Department of Neurology, Istanbul, Turkey.

Background: The main objective was to evaluate and compare the local genotoxicity of sevoflurane and desflurane in bronchoalveolar cells, while the secondary outcome was to detect systemic oxidative DNA damage. To our knowledge, our study is the first one to evaluate the local effects of inhalation anesthetics in human bronchoalveolar cells in patients.

Methods: American Society of Anesthesiologists group I-II patients scheduled for lumbar discectomy surgery were enrolled in this randomized prospective study. Patients were randomized to sevoflurane or desflurane for anesthesia maintenance. Bronchoalveolar lavage samples and peripheral blood samples were taken at 2-time points: the first point (baseline, T1); and the second point (postexposure, T2). Final number of 48 samples were the sevoflurane (n = 22) and desflurane (n = 26) groups. Comet assay was applied to examine genotoxic properties. Oxidative DNA damage in plasma was measured with 8-hydroxy-2'-deoxyguanosine (8-OHdG).

Results: T2 values were higher than baseline values in both the desflurane group (tail-length: 66 ± 24, %DNA in tail: 72 ± 60, tail moment: 47.52 ± 14.4; P = .001, P = .005, P = .001, respectively) and the sevoflurane group (tail-length: 58 ± 33, %DNA in tail: 88 ± 80, tail moment: 51.04 ± 26.4; P = .001, P = .012, P = .001, respectively). T2 plasma 8-OHdG levels were also higher than baseline levels in the desflurane group (3.91 ± 0.19 ng/ml vs 1.32 ± 0.20 ng/ml, P = .001) and sevoflurane group (3.98 ± 0.18 ng/ml vs 1.31 ± 0.11 ng/ml, P = .001). There were no differences between the 2 groups in comet parameters and 8-OHdG levels.

Conclusion: Our results indicate that both inhalation agents cause DNA damage in the bronchoalveolar cells. Also, we detected increases in plasma 8-OHdG concentrations. Local genotoxicity and systemic oxidized DNA damage were similar in both groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000016518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708896PMC
August 2019

Case Report: a novel chromosomal insertion, 46, XY, inv ins(18;2)(q11.2;q13q22), in a patient with infertility and mild intellectual disability.

F1000Res 2019 12;8:281. Epub 2019 Mar 12.

Department of Medical Genetics of Internal Diseases, Istanbul Medical Faculty, İstanbul University, İstanbul, Turkey.

Infertility is an important health problem affecting 15% of couples worldwide. Intellectual disability (ID) is characterized with significant impairment of intellectual function, adaptive daily life skills and social skills. Insertion is a rare chromosomal rearrangement causing infertility and ID. Here, we report a 39-year-old man presenting with primary infertility and mild ID. The patient's spermiogram was consistent with azoospermia. Conventional cytogenetic analysis showed a novel inversion/insertion type of chromosomal aberration involving chromosomes 18 and 2: 46, XY, inv ins(18;2)(q11.2;q13q22). We carried out the array comparative genomic hybridization analysis to confirm the cytogenetic findings. Y micro-deletion analysis demonstrated that the AZF region as intact. We suggest that the novel insertion found in this case [46, XY, inv ins(18;2)(q11.2;q13q22)] may have caused infertility and mild ID in our patient. To the best of our knowledge, this chromosomal insertion has not previously been reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/f1000research.18455.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567292PMC
June 2020

The Effect of PAI-1 Gene Variants and PAI-1 Plasma Levels on Development of Thrombophilia in Patients With Klinefelter Syndrome.

Am J Mens Health 2018 11;12(6):2152-2156

1 Department of Medical Genetics, İstanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine, İstanbul, Turkey.

Klinefelter syndrome (KS) is a common sex chromosome-related abnormality seen among men. KS negatively affects spermatogenesis and testosterone production. It increases the risk of thrombosis but its molecular mechanism has not been well described yet. Elevated PAI-1 is a risk factor for thrombosis. The rs1799889 polymorphism located in the promoter region of the PAI-1 gene was detected in patients with deep venous thrombosis. In this study, the PAI-1 gene variant and its plasma levels in KS patients were examined. Forty-one KS patients (47, XXY) and 50 age-matched healthy controls participated. DNA was isolated from peripheral blood and a real-time PCR method was used to detect known SNPs in the PAI-1 gene. In addition, PAI-1 plasma levels were measured by using ELISA method. There was no significant difference between PAI-1 gene polymorphisms of KS patients and controls ( p > .05). The significant difference was observed in PAI-1 plasma levels between two groups (high PAI-1 plasma level in KS patients compared to controls). The patients' group mean was 55.13 and control group mean in PAI-1 level was 29.89 ng/ml ( p = .020). Clinical features related to thromboembolism especially varicose veins were detected in KS patients frequently ( p = .04). These results suggest that thromboembolism related to clinical features is seen more frequently in cases with KS, but it may not be dependent only on the PAI-1 gene polymorphism structure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1557988318801158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199429PMC
November 2018

Investigation of Gene Expressions of Myeloma Cells in the Bone Marrow of Multiple Myeloma Patients by Transcriptome Analysis

Balkan Med J 2019 01 6;36(1):23-31. Epub 2018 Aug 6.

Department of Internal Medicine, Division of Medical Genetics, İstanbul Universiy İstanbul School of Medicine, İstanbul, Turkey

Background: Multiple myeloma is a plasma cell dyscrasia characterized by transformation of B cells into malignant cells. Although there are data regarding the molecular pathology of multiple myeloma, the molecular mechanisms of the disease have not been fully elucidated.

Aims: To investigate the gene expression profiles in bone marrow myeloma cells via RNA-sequencing technology.

Study Design: Cell study.

Methods: Myeloma cells from four patients with untreated multiple myeloma and B cells from the bone marrow of four healthy donors were sorted using a FACSAria II flow cytometer. The patient pool of myeloma cells and the control pool of B cells were the two comparative groups. A transcriptome analysis was performed and the results were analyzed using bioinformatics tools.

Results: In total, 18.806 transcripts (94.4%) were detected in the pooled multiple myeloma patient cells. A total of 992 regions were detected as new exon candidates or alternative splicing regions. In addition, 490 mutations (deletions or insertions), 1.397 single nucleotide variations, 415 fusion transcripts, 132 frameshift mutations, and 983 fusions, which were reported before in the National Center for Biotechnology Information, were detected with unknown functions in patients. A total of 35.268 transcripts were obtained (71%) (25.355 transcripts were defined previously) in the control pool. In this preliminary study, the first 50 genes were analyzed with the MSigDB, Enrichr, and Panther gene set enrichment analysis programs. The molecular functions, cellular components, pathways, and biological processes of the genes were obtained and statistical values were determined using bioinformatics tools and are presented as a supplemental file.

Conclusion: , and are identified as possible candidate genes associated with myelomagenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4274/balkanmedj.2018.0356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335938PMC
January 2019

REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis.

Am J Hum Genet 2017 Jul;101(1):149-156

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:

Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15) have been mapped to autosomes and one gene (SOS1) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern. Here we report 11 individuals with HGF from three unrelated families. Whole-exome sequencing (WES) revealed three different truncating mutations including two frameshifts and one nonsense variant in RE1-silencing transcription factor (REST) in the probands from all families and further genetic and genomic analyses confirmed the WES-identified findings. REST is a transcriptional repressor that is expressed throughout the body; it has different roles in different cellular contexts, such as oncogenic and tumor-suppressor functions and hematopoietic and cardiac differentiation. Here we show the consequences of germline final-exon-truncating mutations in REST for organismal development and the association with the HGF phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2017.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501868PMC
July 2017

Roles of Signal Transducer Pathways in Investigation of Biopsies from Patients with Bladder Tumors

Asian Pac J Cancer Prev 2017 01 1;18(1):201-205. Epub 2017 Jan 1.

Department of Internal Medicine, Division of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. and

Background:The process of development of bladder cancer features alteration of normal biological conditions caused by changes in molecular pathways. Removing control over regulation of these pathways could lead to changes in signal transduction and abnormal regulation of genes. During tumor formation and progression, genes regulate critical cellular processes, involved in cell cycling, growth and death. Here we evaluated the expression and prognostic importance of FGFR1, HRAS, CCND1, CCND3, STAT3 and FAS genes. Methods: Tumor tissues of 44 patients diagnosed with bladder cancer were investigated for changes in expression levels of FGFR1, HRAS, CCND1, CCND3, FAS and STAT3 genes by the RT-PCR method. Signal transduction pathways and expression of individual genes related to these pathways were analyzed using the “One Sample Test”. Results: There were statistically significant changes in the expression levels of HRAS, CCND1, CCND3 and STAT3, but not FGFR1 and FAS genes. Examination of associations with age, gender, smoking, chemotherapy, tumor grade and tumor growth pattern using the “Independent Samples Test”, showed importance relations between the CCND1 gene and cigarette smoking and sex. Conclusion: Over-expression of HRAS, CCND1, CCND3 and STAT3 genes may play roles in bladder cancer development and progression, while cigarette smoking is significantly associated with CCND1 gene expression and consequently concluded to be contributing to the development of bladder cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22034/APJCP.2017.18.1.201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563101PMC
January 2017

WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects.

Hum Mutat 2017 01 7;38(1):7-15. Epub 2016 Oct 7.

Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237432PMC
January 2017

Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction.

Gastroenterology 2015 Apr 6;148(4):771-782.e11. Epub 2015 Jan 6.

Department of Medical and Surgical Sciences, University of Bologna, and St. Orsola-Malpighi Hospital, Bologna, Italy; Centro Unificato di Ricerca Biomedica Applicata, Bologna, Italy. Electronic address:

Background & Aims: Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers.

Methods: We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed.

Results: We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens.

Conclusions: Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2014.12.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375026PMC
April 2015

Genotoxicity of fixation devices analyzed by the frequencies of sister chromatid exchange.

Ulus Travma Acil Cerrahi Derg 2013 Jul;19(4):299-304

Department of Oral and Maxillofacial Surgery, İstanbul University Faculty of Dentistry, İstanbul, Turkey.

Background: Metal alloys utilized in the management of jaw fractures may exert genotoxic effects. Our purpose was to compare the genotoxicity of intermaxillary fixation devices containing nickel and chromium to that of titanium miniplates utilized in treatment of jaw fractures through the analysis of sister chromatid exchange.

Methods: In this prospective study, in a total of 28 non-smoker patients (10 females, 18 males; mean age 33.43±10.76; range 15 to 60 years) with jaw fractures, 14 were treated with intermaxillary fixation by administration of nickel-chromium wire and arch bar and 14 with titanium miniplates to investigate the genotoxicity of different metal alloys. The outcome variable was the frequency of sister chromatide exchange in peripheral lymphoctyes, determined through the analysis of venous blood samples obtained preoperatively and 4 to 6 weeks postoperatively.

Results: The frequency of the average sister chromatid exchange was found to be significantly higher in patients treated with the nickel-chromium intermaxillary fixation devices than those treated by titanium miniplates (1.29±0.29 vs. 0.46±0.39, p<0.001).

Conclusion: Although titanium miniplate osteosynthesis is an invasive technique in comparison with the nickel-chromium-containing intermaxillary fixation devices, titanium seems to exert less genotoxic effect than the nickel-chromium alloy. However, this finding should be supported in clinical studies with a larger sampling size.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5505/tjtes.2013.64176DOI Listing
July 2013

A Turkish trichothiodystrophy patient with homozygous XPD mutation and genotype-phenotype relationship.

J Dermatol 2012 Dec 5;39(12):1016-21. Epub 2012 Oct 5.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

Trichothiodystrophy (TTD) is a rare, recessive condition involving multiple organs and systems. Four genes associated with nuclear excision repair have been described in the molecular etiology of TTD. There is a significant heterogeneity of clinical and laboratory findings of TTD, even in individuals carrying the same mutation. Worldwide, approximately 120 cases have been reported, mostly from Western populations and the mutations are compound heterozygous. We herein present clinical and laboratory findings of a female patient with a homozygous mutation, R722W, in the XPD gene. To date, two patients who carry the same mutation have been reported. Our genotype-phenotype correlation study showed patients who carry R722W mutation have a more severe TTD phenotype than other types of mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1346-8138.2012.01662.xDOI Listing
December 2012

Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis.

Hum Mutat 2012 Aug 29;33(8):1175-81. Epub 2012 May 29.

School of Medicine, University of Leeds, Leeds, United Kingdom.

Pachydermoperiostosis, or primary hypertrophic osteoarthropathy (PHO), is an inherited multisystem disorder, whose features closely mimic the reactive osteoarthropathy that commonly accompanies neoplastic and inflammatory pathologies. We previously described deficiency of the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD) as a cause of this condition, implicating elevated circulating prostaglandin E(2) (PGE(2)) as causative of PHO, and perhaps also as the principal mediator of secondary HO. However, PHO is genetically heterogeneous. Here, we use whole-exome sequencing to identify recessive mutations of the prostaglandin transporter SLCO2A1, in individuals lacking HPGD mutations. We performed exome sequencing of four probands with severe PHO, followed by conventional mutation analysis of SLCO2A1 in nine others. Biallelic SLCO2A1 mutations were identified in 12 of the 13 families. Affected individuals had elevated urinary PGE(2), but unlike HPGD-deficient patients, also excreted considerable quantities of the PGE(2) metabolite, PGE-M. Clinical differences between the two groups were also identified, notably that SLCO2A1-deficient individuals have a high frequency of severe anemia due to myelofibrosis. These findings reinforce the key role of systemic or local prostaglandin excess as the stimulus to HO. They also suggest that the induction or maintenance of hematopoietic stem cells by prostaglandin may depend upon transporter activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.22111DOI Listing
August 2012

The co-presence of deletion 7q, 20q and inversion 16 in therapy-related acute myeloid leukemia developed secondary to treatment of breast cancer with cyclophosphamide, doxorubicin, and radiotherapy: a case report.

J Med Case Rep 2012 Feb 16;6:67. Epub 2012 Feb 16.

Istanbul University Istanbul Medical Faculty, Department of Internal Medicine, Division of Hematology, Istanbul, Turkey.

Introduction: Therapy-related acute myeloid leukemia occurs as a complication of treatment with chemotherapy, radiotherapy, immunosuppressive agents or exposure to environmental carcinogens.

Case Presentation: We report a case of therapy-related acute myeloid leukemia in a 37-year-old Turkish woman in complete remission from breast cancer. Our patient presented to our facility with fatigue, fever, sore throat, peripheral lymphadenopathy, and moderate hepatosplenomegaly. On peripheral blood and bone marrow aspirate smears, monoblasts were present. Immunophenotypic analysis of the bone marrow showed expression of CD11b, CD13, CD14, CD15, CD33, CD34, CD45 and human leukocyte antigen-DR, findings compatible with the diagnosis of acute monoblastic leukemia (French-American-British classification M5a). Therapy-related acute myeloid leukemia developed three years after adjuvant chemotherapy consisting of an alkylating agent, cyclophosphamide and DNA topoisomerase II inhibitor, doxorubicin and adjuvant radiotherapy. Cytogenetic analysis revealed a 46, XX, deletion 7 (q22q34), deletion 20 (q11.2q13.1) karyotype in five out of 20 metaphases and inversion 16 was detected by fluorescence in situhybridization. There was no response to chemotherapy (cytarabine and idarubicin, FLAG-IDA protocol, azacitidine) and our patient died in the 11th month after diagnosis.

Conclusions: The median survival in therapy-related acute myeloid leukemia is shorter compared to de novoacute myeloid leukemia. Also, the response to therapy is poor. In therapy-related acute myeloid leukemia, complex karyotypes have been associated with abnormalities of chromosome 5, rather than 7. To the best of our knowledge, this is the first case of therapy-related acute myeloid leukemia showing the co-presence of deletion 7q, 20q and the inversion 16 signal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1752-1947-6-67DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327634PMC
February 2012

Investigation of Arg399Gln and Arg194Trp polymorphisms of the XRCC1 (x-ray cross-complementing group 1) gene and its correlation to sister chromatid exchange frequency in patients with chronic lymphocytic leukemia.

Genet Test Mol Biomarkers 2012 Apr 22;16(4):287-91. Epub 2011 Nov 22.

Department of Internal Medicine, Division of Medical Genetics, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey.

Polymorphisms of the x-ray repair cross-complementing group 1 (XRCC1) gene have been reported to be associated with various forms of cancer. We evaluated the possible effects of the Arg194Trp and the Arg399Gln polymorphisms on the risk for chronic lymphocytic leukemia (CLL) in 73 patients and 50 controls. We also analyzed their relation to frequency of sister chromatid exchange (SCE). With respect to codon 194, the allelic frequency of the Arg194Trp polymorphism did not significantly differ between the 2 groups. The proportion of individuals carrying the Arg194Trp polymorphism was not different in the 2 groups. With respect to codon 399, the proportion of the individuals carrying the Arg399Gln allele (90% vs 62%; p=0.000; odds ratio [OR], 5.779; 95% confidence interval [CI], 2.2-15.183) and the allelic frequency of the Arg399Gln polymorphism (56% vs 36%; p=0.002; OR, 2.278; 95% CI, 1.350-3.843) was significantly higher in the patient group. The frequency of the Arg/Gln genotype was significantly higher in the patient group (68.50% vs 52%; p=0.049; OR, 2.007; 95% CI, 0.955-4.217). The mean SCE frequency in the patient group was significantly higher (9.2±4 vs 7.5±2; p=0.02). When different compound genotypes were compared, the coexistence of Arg/Arg genotype in codon 194 with Arg/Arg genotype in codon 399 was significantly more frequent in the control group (30% vs 9%; p=0.004; OR, 0.247; 95% CI, 0.092-0.664). Within the patient group, SCE frequency did not differ between patients with various genotypes. The Arg399Gln polymorphism may be etiologically associated with CLL; however, it does not seem to increase SCE frequency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2011.0152DOI Listing
April 2012

Comparison of the cytogenetic and molecular analyses in the assessment of imatinib response in chronic myelocytic leukemia.

Genet Test Mol Biomarkers 2009 Oct;13(5):599-602

Division of Medical Genetics, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

We aimed to compare the cytogenetic and molecular analyses in the assessment of imatinib mesylate response in patients suffering the chronic phase of chronic myelocytic leukemia who were refractory to alpha-interferon treatment. A total of 117 patients in the chronic phase of chronic myelocytic leukemia were included. The patients were treated with 400 mg/day imatinib mesylate. Bone marrow samples were obtained for the cytogenetic and molecular analyses. Patients without the Ph chromosome were defined as complete cytogenetic responders. Partial cytogenetic response was determined when the Ph chromosome was detected in 1-35% of the cells. Molecular response was determined by quantitative real-time reverse transcriptase polymerase chain reaction (QR-PCR) and defined as no detection of BCR-ABL mRNA. The frequencies of complete and partial cytogenetic response were 29% (n = 34) and 15% (n = 18), respectively. No cytogenetic response was achieved in 56% (n = 65) of the patients. Molecular response was achieved in 62% (n = 21) and 33% (n = 6) of the complete and partial cytogenetic responders, respectively. All of the 65 patients with no cytogenetic response were also molecular nonresponders. We conclude that there is reasonable agreement between the cytogenetic and molecular analyses. Both methods are complementary in the assessment of response to therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2009.0055DOI Listing
October 2009

Left ventricular thickness is increased in nonhypertensive Turner's syndrome.

Echocardiography 2009 Sep 26;26(8):943-9. Epub 2009 May 26.

Department of Cardiology, Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Background: Turner's syndrome (TS), the most frequent congenital anomaly in newborn girls, is associated with various cardiovascular abnormalities, predominantly bicuspid aortic valves and aortic coarctation. The causes of the left ventricular hypertrophy (LVH) and ECG findings associated with TS are unknown. We used echocardiography to assess cardiac structure and function in normotensive patients with TS.

Method: Thirty-one patients with TS and 30 healthy women were enrolled in this comparative study. Twelve-lead ECG, 24-hour-ambulatory ECG recording, and echocardiography were performed.

Results: With 24-hour-ambulatory ECG recording, the mean heart rate (HR) of TS women was higher than non-TS women. With echocardiographic examination, the interventricular septum diastolic thickness, left ventricle posterior wall diastolic thickness (LVPW), the LV mass index (LVMI), and left atrial diameter index (LADi) were significantly higher in TS women compared with controls. Mitral flow A velocity was significantly higher and the ratio of early to late diastolic filling was significantly lower in TS patients.

Conclusion: HR, LV wall thicknesses, LVMI and the LADi are significantly increased in normohypertensive TS women. There is also subclinical diastolic dysfunction in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1540-8175.2009.00902.xDOI Listing
September 2009

Adult height in Turkish patients with Turner syndrome without growth hormone treatment.

Turk J Pediatr 2008 Sep-Oct;50(5):415-7

Department of Pediatrics, Marmara University Faculty of Medicine, Istanbul, Turkey.

Spontaneous adult height (AH) in Turner syndrome (TS) varies among populations. Population-specific AH data is essential to assess the efficacy of growth-promoting therapies in TS. A multicenter study was performed to establish AH of nongrowth hormone (GH)-treated Turkish patients with TS. One hundred ten patients with TS (diagnosed by karyotype) who reached AH (no growth in the previous year, or bone age > 15 years) without receiving GH treatment were included in the study. The average AH was found to be 141.6 +/- 7.0 cm at the age of 22.9 +/- 6.2 years, which is 18.4 cm below the population average and 16.4 cm below the patients' mid-parental heights. Bone age at start of estrogen replacement was 12.3 +/- 1.3 year. Karyotype distribution of the patients was 45X (43%), 45X/46XX (16%), 45X/46Xi (12%), 45XiXq (10%) and others (19%). When the patients were evaluated according to their karyotype as 45X and non-45X, no significant difference in AH was observed (142.4 +/- 6.9 cm vs 140.9 +/- 7.1 cm, respectively). Adult height of non-GH-treated Turkish TS patients obtained in this study was comparable to that of other Mediterranean populations, but shorter than that of Northern European patients. Karyotype does not seem to affect AH in TS.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2009

The effects of etodolac, nimesulid and naproxen sodium on the frequency of sister chromatid exchange after enclused third molars surgery.

Yonsei Med J 2008 Oct;49(5):742-7

Department of Oral Surgery, Istanbul University, Faculty of Dentistry, Istanbul, Turkey.

Purpose: Non-steroidal anti-inflammatory drugs (NSAID) are frequently used in oral surgical procedures in dentistry. The evaluation of the frequency of sister chromatid exchange (SCE) is accepted as a reliable cytogenetic method to assess the genotoxic effects of environmental factors.

Materials And Methods: In this study, the genotoxic effects of various NSAIDs were assessed in 30 patients to who they were administered following encluosed third molar surgery using SCE analysis before and after the operation. The frequency of SCE was evaluated before the operation and after 3 days of etodolac, nimesulid and naproxen use.

Results: There was no statistically significant difference in the frequency of SCE between the preoperative and postoperative states in patients given etodolac, nimesulid or naproxen sodium.

Conclusion: Short term use of selective and non-selective NSAIDs was not associated with a significant genotoxic effect that could be detected using the SCE method in peripheric lymphocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3349/ymj.2008.49.5.742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615361PMC
October 2008

Atrial and ventricular arryhthmogenic potential in Turner Syndrome.

Pacing Clin Electrophysiol 2008 Sep;31(9):1140-5

Department of Cardiology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey.

Background: P-wave dispersion (Pd), corrected P-wave dispersion (Pdc), QT-wave dispersion (QTd), and corrected QT-wave dispersion (QTdc) parameters were not assessed in Turner Syndrome (TS) before. The aim of this study is to investigate the cardiac arrhythmogenic potential in patients with TS.

Methods: Thirty-one patients with TS and 30 healthy women were enrolled in the study. For this purpose 12-lead electrocardiogram (ECG) and 24-hour ambulatory ECG recordings were performed.

Results: Pd, Pdc, QTd, and QTdc were significantly higher in patients with TS. On 24-hour ambulatory ECG recording, the mean heart rate (HR) was higher, while the mean of all RR intervals between normal beats (MeanNN), the standard deviation of all the RR intervals (SDNN), the square root of the mean of the squared differences of two consecutive RR intervals (rMSSD), and the percentage of the beats with consecutive RR interval difference more than 50 milliseconds (pNN50) were lower in TS.

Conclusion: There were significant increases in Pd, Pdc, QTd, and QTdc in patients with TS and they may be features of the disease. The frequency of supraventricular arrhythmias was increased. There also was a significant deterioration of sympathetic and parasympathetic components of autonomic function as assessed by heart rate variability (HRV) in Turner patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1540-8159.2008.01154.xDOI Listing
September 2008

Effect of cyclosporin A and tacrolimus on sister chromatid exchange frequency in renal transplant patients.

Genet Test 2008 Sep;12(3):427-30

Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Long-term use of Cyclosporin A (CsA) and Tacrolimus is known to yield serious untoward side effects including nephrotoxicity, neurotoxicity, and malignant tumor formation. Sister chromatid exchange (SCE) is used to assess the genotoxic potential of various agents. A total of 37 postrenal transplant patients receiving either CsA (n = 20) or Tacrolimus (n = 17) were included in this study. The genotoxic effects of CsA and Tacrolimus were assessed by determination of SCE frequency. In patients receiving CsA, SCE frequency was increased significantly compared to that in the control group (p = 0.001), whereas Tacrolimus did not yield such a significant change (p = 0.801). SCE frequency was not correlated with drug dosage (p > 0.05). Our results indicate that the use of CsA, but not Tacrolimus 506, is associated with an increased genotoxic effect in postrenal transplant patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gte.2008.0006DOI Listing
September 2008

Loss of heterozygosity at chromosome 14q is associated with poor prognosis in head and neck squamous cell carcinomas.

J Cancer Res Clin Oncol 2008 Dec 3;134(12):1267-76. Epub 2008 Jun 3.

Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho 2-5-1, Okayama 700-8525, Japan.

Purpose And Methods: Loss of heterozygosity (LOH) in a chromosomal location indicates the presence of an inactivated tumor suppressor gene (TSG). Inactivation of TSG has a functional role in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Based on the recent evidences of a putative TSG on chromosome 14, we examined LOH on chromosome 14q using eight polymorphic microsatellite markers in 50 cases of HNSCCs.

Results: Three regions were detected to have a high LOH rate which included 14q21.2-22.3 (42.5%), 14q31 (55%), and 14q32.1 (37%). The correlation between LOH and clinicopathological findings was investigated through statistical analyses. A strong correlation was observed between the highest LOH marker and the overall and disease-free survival.

Conclusions: The results suggest that the distal part of chromosome 14 may host a TSG that may lead to the development and/or progression of HNSCCs. Several genes such as CHES1, BMP4, SAV, and PNN have arisen as candidate tumor suppressors in the region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-008-0423-1DOI Listing
December 2008

Acute megakaryoblastic leukemia mimicking small round cell tumor with novel t(1;5)(q21;p13).

APMIS 2008 Feb;116(2):163-6

Marmara University School of Medicine, Department of Pathology, Istanbul, Turkey.

Acute megakaryoblastic leukemia is a relatively rare form of acute leukemia that has heterogeneous blast morphology and karyotypic abnormalities. An 8-month-old boy with a retroperitoneal mass was diagnosed as having acute megakaryoblastic leukemia that initially presented as small round cell tumor of childhood. Bone marrow aspiration showed syncytial groups of atypical medium sized cells with scant cytoplasm and fine nuclear chromatin. Retroperitoneal mass biopsy showed several lymph nodes with cohesive clusters of neoplastic cells that demonstrated expression of Factor VIII. Flow cytometric analysis of the second bone marrow aspiration showed CD 61 positivity. Karyotypic analysis of bone marrow cells showed a novel translocation, (1;5)(q21;p13).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1600-0463.2008.00780.xDOI Listing
February 2008

Lens opacities in Bloom syndrome: case report and review of the literature.

Ophthalmic Genet 2007 Sep;28(3):175-8

Istanbul University, Istanbul Medical Faculty, Department of Internal Medicine, Division of Medical Genetics, Istanbul, Turkey.

Bloom syndrome is an autosomal recessive disorder characterized by proportionate short stature, photosensitivity, immunodeficiency, hypogonadism and a tendency to develop various malignancies. The greatly increased frequency of sister chromatid exchanges (reciprocal exchange of homologous segments between the two sister chromatids of a chromosome) is regarded as pathognomonic for BS. We describe an 18-year old girl who presented with short stature. She was diagnosed with BS based on an extremely increased frequency of sister chromatid exchanges. Ophthalmological examination revealed mild lens opacities bilaterally, which, to our knowledge, has not been previously reported to be associated with BS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13816810701389685DOI Listing
September 2007

The genotoxic effects in lymphocyte cultures of children treated with radiosynovectomy by using yttrium-90 citrate colloid.

Cancer Biother Radiopharm 2007 Jun;22(3):393-9

Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Unlabelled: The aim of this study was to investigate the genotoxic effect on the peripheral blood lymphocytes potentially induced by yttrium-90 citrate colloid (Y-90) in children who were undergoing radiosynovectomy for hemophilic synovitis, using chromosomal aberration analysis (CA) and the micronuclei (MN) assay for detecting chromosomal aberrations, as well as the sister chromatid exchanges (SCE) technique for assessed DNA damage.

Materials And Methods: Cytogenetic analyses were undertaken in 18 boys (mean age, 14.5 +/- 2.1 years) with hemophilic synovitis who underwent radiosynovectomy with Y-90. CA, MN, and SCE were evaluated just prior to, then at 2 and 90 days following radiosynovectomy from the peripheral lymphocytes of the children. An activity of 185 MBq of Y-90 was injected into the 18 knee joints under aseptic conditions. To check the possibility of leakage from the joint and its migration within the body, the patients underwent scanning under a dual-headed gamma camera at the hours 2 and 48 following the procedure.

Results: The procedure was well tolerated in all the children, and there was no extra-articular activity owing to extra-articular leakage of radioactive material in whole-body imaging. The mean frequency of CA in lymphocytes determined prior to the onset of therapy (0.31 +/- 0.48/900 cells) was not significantly increased, in comparison to the control values obtained 2 (0.30 +/- 0.48/900 cells) and 90 days (0.15 +/- 0.37/900 cells) after radiosynovectomy (p = 1.0 and 0.625, respectively). We observed that MN frequency was mildly increased in lymphocytes 2 days after therapy (8.30 +/- 1.89 MN/1000 binucleated cells vs. 9.23 +/- 1.79 MN/1000 binucleated cells; p = 0.013). But there was no significant difference between the baseline and the day 90 control levels of MN (p = 0.196). In the analysis of SCE frequency, there were no significant differences between the baseline (8.11 +/- 0.77) and the control analysis performed 2 and 90 days following radiosynovectomy (8.18 +/- 0.77 and 8.07 +/- 0.74; p = 0.710 and 0.662, respectively).

Conclusions: The results of this study indicated that high radiation doses are not obtained by peripheral lymphocytes of children who undergo Y-90 radiosynovectomy and, therefore, they contradict a high cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/cbr.2006.328DOI Listing
June 2007

Treatment of acquired severe aplastic anemia with antilymphocyte globulin, cyclosporin A, methyprednisolone, and granulocyte colony-stimulating factor.

Am J Hematol 2007 Sep;82(9):783-6

Division of Hematology, Istanbul Faculty of Medicine, Istanbul University, 34390, Capa, Istanbul, Türkiye.

Fifty-six adult patients with newly diagnosed acquired severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), methylprednisolone (Mpred), granulocyte colony-stimulating factor (G-CSF) as first-line therapy. The median age was 34 (range, 17-72) and median neutrophil count 0.280 x 10(9)/L. Trilineage hematologic recovery (at a median interval of 105 days from treatment) was seen in 46 patients (37 complete, 9 partial) after one (n = 38) or two (n = 8) courses of ALG. Cytogenetic abnormalities were observed in three unresponders, clonal hematologic disease in three complete responders, and relapse of marrow aplasia in four complete responders. Median follow up for surviving patients was 1,668 days (range, 237-4,012). The actuarial survival at 5 years was 82%, falling to 77.1% at 7 years and was stationary at 7 and 8 years. Survival was not influenced by the neutrophil count (72% vs. 87%, for neutrophils less than vs. greater than 0.2 x 10(9)/L; P = 0.54). Immunosuppressive treatment of SAA with the 4-drug combination appears to be effective. The significant prognostic effect of an enduring increase of the white blood cell (WBC) count during G-CSF treatment may suggest complete and partial response to therapy. In nonresponders, the WBC count either did not change or elevated values gradually returned to nearly their initial levels while the patients were still under G-CSF treatment. In patients not responsive to treatment but living under CyA and G-CSF, the possibility of developing cytogenetic abnormalities does not seem to be low, despite the absence of findings attributable to manifest myelodysplastic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.20954DOI Listing
September 2007

A novel locus for syndromic chronic idiopathic intestinal pseudo-obstruction maps to chromosome 8q23-q24.

Eur J Hum Genet 2007 Aug 9;15(8):889-97. Epub 2007 May 9.

Laboratory of Medical Genetics, Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy.

Chronic idiopathic intestinal pseudo-obstruction (CIIP) is a rare and severe clinical syndrome characterized by symptoms and signs of intestinal occlusion, in the absence of any mechanical obstruction of the gut lumen. In the attempt to identify the genetic basis of CIIP, we analyzed a Turkish pedigree with a high degree of consanguinity in which three siblings presented with a syndromic form of CIIP. All affected family members were characterized by recurrent, self-limiting subocclusive episodes, long-segment Barrett esophagus, and a variety of minor cardiac valve or septal defects. In some patients full-thickness intestinal biopsy samples were obtained and tissues were processed for immunohistochemistry using antibodies to different markers of the intestinal neuromuscular tract. Full-thickness biopsies of the gut wall showed abnormalities of both the neural and muscular components suggesting an underlying intestinal neuro-myopathy. Blood samples were collected for DNA extraction from each available family member and DNAs were genotyped using 382 microsatellites spanning the entire genome with the aim to take advantage of the homozygosity mapping approach. Linkage analysis identified a new syndromic locus on chromosome 8q23-q24 (multipoint LOD score=5.01). Our data strongly support the presence of a new genetic locus associated with CIIP, long-segment Barrett esophagus, and cardiac involvement on chromosome 8.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/sj.ejhg.5201844DOI Listing
August 2007

Comparison of rheological parameters in patients with post hepatitic and alcoholic cirrhosis.

Clin Hemorheol Microcirc 2007 ;36(3):247-52

Istanbul University, Istanbul Medical Faculty, Department of Physiology, Istanbul, Turkey.

It is well known that various constituents of blood, especially lipids and proteins, and hematological parameters are altered in chronic liver diseases. These alterations have been shown to affect rheological parameters in various studies. However, it is not clear whether the etiology of chronic liver has any specific influence on flow dynamics of blood. In the present study, we analysed erythrocyte rigidity (ER), whole blood and plasma viscosity, and other factors related to blood rheology (including hematological parameters, plasma lipids and proteins) in healthy controls (n=20) and patients with post hepatitic and alcoholic cirrhosis (n=15 in each group). ER was significantly higher (p<0.05) in both groups compared to controls. Although blood viscosity was found to be low in both groups, the difference reached statistical significance only in patients with alcoholic cirrhosis. On the other hand, when compared to controls, plasma viscosity was significantly lower in patients with alcoholic cirrhosis and significantly higher in patients with posthepatitic cirrhosis (p<0.05). When we compare post hepatic and alcoholic cirrhosis with each other, there was no significant difference in ER between the two groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2007

Increased sister chromatid exchange frequency in young women with breast cancer and in their first-degree relatives.

Cancer Genet Cytogenet 2006 Nov;171(1):65-7

Division of Medical Genetics, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.

The well-known increased risk of breast cancer (BC) in first-degree relatives of patients with BC has been related to shared genetic factors including defective DNA repair, with loss of genomic integrity. On the other hand, it can be hypothesized that early-onset breast cancer is also associated with overburden of heritable factors leading to increased DNA injury. In this respect, we analyzed sister chromatid exchange frequency (SCE) in 20 women with breast cancer (all < or =40 years old), in their first-degree female relatives, and in 20 age-matched healthy females without a personal or family history of cancer. SCE was significantly increased (P < 0.05) in patients (7.17 +/- 1.81 per metaphase) and in their first-degree relatives (6.44 +/- 0.98), compared with controls (5.85 +/- 0.72). There was no difference in SCE frequency between patients and their first-degree relatives. We suggest that the increased SCE in patients reflects a genomic instability that may be operative in carcinogenesis. Further, genomic instability is shared also by first-degree relatives, although none of them had a history of breast cancer at the time of the study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cancergencyto.2006.06.005DOI Listing
November 2006

A case of myelodysplastic syndrome with erythroid hypoplasia associated with a familial translocation t(3;14)(p21.1;q24.1).

Am J Hematol 2006 Nov;81(11):883-7

Division of Hematology, Department of Internal Medicine, Istanbul Medical School, Istanbul University, 34390 Capa Istanbul, Turkey.

Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has not yet been clearly defined. We report here a 20-year-old woman with severe transfusion-dependent anemia and reticulocytopenia. White blood cells and platelet counts were normal. Bone marrow examination showed a low percentage of erythroid precursors (6%) and a marked dyserythropoiesis and dysmegakaryopoiesis. A diagnosis of MDS (refractory anemia according to the FAB classification) with erythroid hypoplasia was made. Cytogenetic analysis of the bone marrow and peripheral blood revealed a 46,XX,t(3;14)(p21.1;q24.1) translocation, which was confirmed by fluorescence in situ hybridization analysis. This translocation was detected in the apparently healthy younger brother, father, and aunt (father's sister) of the patient. Clonality of T cells in the patient was not confirmed by the polymerase chain reaction and heteroduplex temperature-gradient gel electrophoresis. IgM serology for B19 parvovirus was negative. Other conditions known to be associated with erythroid hypoplasia, such as thymoma, were not present. The patient failed to respond to immunosuppressive therapy (antithymocyte globulin and cyclosporin A). Administration of recombinant human erythropoietin improved her anemia. To our knowledge, this balanced translocation, namely t(3;14)(p21.1;q24.1), which is present both in the patient with MDS with erythroid hypoplasia and in the healthy members of the family, has not been defined previously.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.20684DOI Listing
November 2006