Karyotype Anomalies Research Articles

Cytogenetic studies on newborns from high and normal level natural radiation areas of Kerala in southwest coast of India

Purpose: To study, characterize and compare chromosome aberrations and karyotype anomalies among newborns from high (> 1.5 mGy/y) and normal (≤ 1.5 mGy/y) level natural radiation areas of monazite-sand bearing southwest coast of Kerala in India.Materials and methods: Cord blood samples from newborns were collected from selected Government hospitals in heparinized vials and cultures were set up employing standard microculture techniques, slides were prepared, coded and stained with giemsa. Well spread metaphases were analyzed for chromosome aberrations and karyotype anomalies.Results: A total of 1,267,788 metaphases from 27,295 newborns of mothers aged 17–45 years (17,298 from high and 9,997 from normal level radiation areas) were analyzed during 1986–2007. Frequencies of dicentrics in high and normal level radiation areas were 1.90 ± 0.14 and 2.01 ± 0.26 per 10,000 cells, respectively (Relative frequency [RF] = 0.94; 95% CI: 0.71–1.26). Karyotype anomalies had a frequency of 5.49‰ and 6.7‰, respectively (RF = 0.82; 95% CI: 0.60–1.12). No dose-related trend was observed in chromosome aberrations or karyotype anomalies.Conclusion: Frequencies of chromosomal aberration and karyotype anomalies between the newborns from the high level natural radiation area (HLNRA) and normal level natural radiation areas (NLNRA) were very similar.

Incidence of Autoimmunity in Patients (pts) with Low-Risk (LR) Myelodysplastic Syndrome (MDS): 10 Years Follow-up

AbstractAbstract 4931 Background:Autoimmunity, evidenced by positive serology or autoimmune diseases, has been noted to co-exist in pts with MDS. Autoimmune dysfunction has been found in some pts with a variant of MDS called hypocellular MDS, where immune suppressant medications have role in treatment. Clinical implications of AI on survival are not well described. Aim:To study clinical influence of autoimmunity on pts with LR-MDS. Methods:All adult pts diagnosed with LR (RCUD, RARS, and RCMD) MDS at the Mayo Clinic between 1996 to 2000 were studied. Retrospective data collection included pts' demographics, laboratory tests, bone marrow biopsies, treatment modalities and survival information. Autoimmunity (AI) was considered present if pts had evidence of positive serological testing (such as rheumatoid factor (RF), anti-nuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA)) and/or were diagnosed with autoimmune diseases (such as rheumatoid arthritis, vasculitis, autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP)). IRB approval was obtained in accordance with Helsinki Declaration. Chi-Square, t-test and Anova were used for comparatives between groups, and Kaplan-Meier test was applied for survival estimates using JMP 9. 0 software. Results:A total of 134 adult pts were found to have LR-MDS at the time of their diagnosis. Sixty-six percent (89) were males, 13% (17) had antecedent hematological disease (AHD), and only 7% (9) had prior radio- or chemotherapy. Thirty-nine (29%) had evidence of AI. At the time of diagnosis, pts’ median Hgb was 9. 3 g/dL, white blood cells (WBC) 4. 1×109/L, and platelets 151×109/L. On comparison, there was no difference between pts with AI (group 1) to the rest of the sample (group 2) (p = 0. 12, 0. 85 and 0. 23, respectively). Bone marrow cytogenetics were abnormal in 42% (56) pts, with 44 pts have one cytological anomaly, and only 2 have four anomalies. Twenty-four pts (18%) had RCUD, 60 (44%) RARS and 50 (37%) RCMD, as defined by World Health Organization (WHO) classification (Vardiman et al, 2008). Karyotype anomalies within the three WHO classes were found in 12/19 pts (63%), 15/52 pts (29%), and in 29/42 pts (70%), respectively. Of note, among those with karyotype anomalies, the mean number of cytogenetic abnormalities was significantly different across the three categories (F=6. 89, p=. 0014), with means of 0. 5, 0. 3, and 0. 9 respectively. Seven pts (5%) progressed into acute myeloid leukemia. Seventy percent of pts (94) remained as stable disease.Of the 134 pts studied, 39 (29%) were found to have evidence of AI, with 24/48 (50%) had abnormal serological tests, and 29/134 (21%) had an autoimmune disease. When tested, positive RF was found in 7/25 (28%), ANA in 14/42 (33%), anti dsDNA in 1/11 (9%), anti SS-A/-B in 2/3 (66%), ANCA in 1/12 (8%), anti-smooth muscle in 1/2 (50%), and anti-histone in 1 pt. As per autoimmune diseases, rheumatoid arthritis was identified in 6 pts (4%), vasculitides in 9 (7%), AIHA in 4 pts (3%), Sjögren syndrome in 3 (2%), myositis in 2 (1. 4%), ITP in 2 pts (1. 4%). There was no difference in AI frequency based on WHO classification (p 0. 17) or based on cytogenetic grouping (p 0. 37). Overall survival in pts with LR-MDS was found to be lower in group 1 as compared to group 2 but did not reach statistical significance (p=0. 109), with median survival of 40 months and 81 months, respectively. Conclusion:AI is a frequent finding in pts with LR-MDS, seen in up to 29% of pts. On comparison there was no difference in hematological parameters of both groups with or without AI (CBC, cytogenetics, and WHO classification). There was no survival difference in LR-MDS pts with AI compared to pts without AI. Larger size studies are needed to confirm our findings. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Identification of a Novel, Recurrent SLC44A1‐PRKCA Fusion in Papillary Glioneuronal Tumor

Mixed neuronal-glial tumors are rare and challenging to subclassify. One recently recognized variant, papillary glioneuronal tumor (PGNT), is characterized by prominent pseudopapillary structures and glioneuronal elements. We identified a novel translocation, t(9;17)(q31;q24), as the sole karyotypic anomaly in two PGNTs. A fluorescence in situ hybridization (FISH)-based positional cloning strategy revealed SLC44A1, a member of the choline transporter-like protein family, and PRKCA, a protein kinase C family member of serine/threonine-specific protein kinases, as the 9q31 and 17q24 breakpoint candidate genes, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) analysis using a forward primer from SLC44A1 exon 5 and a reverse primer from PRKCA exon 10 confirmed the presence of a SLC44A1-PRKCA fusion product in both tumors. Sequencing of each chimeric transcript uncovered an identical fusion cDNA junction occurring between SLC44A1 exon 15 and PRKCA exon 9. A dual-color breakpoint-spanning probe set custom-designed for interphase cell recognition of the translocation event identified the fusion in a third PGNT. These results suggest that the t(9;17)(q31;q24) with the resultant novel fusion oncogene SLC44A1-PRKCA is the defining molecular feature of PGNT that may be responsible for its pathogenesis. The FISH and RT-PCR assays developed in this study can serve as valuable diagnostic adjuncts for this rare disease entity.

Novel Fusion of MYST/Esa1-Associated Factor 6 and PHF1 in Endometrial Stromal Sarcoma

Rearrangement of chromosome band 6p21 is recurrent in endometrial stromal sarcoma (ESS) and targets the PHF1 gene. So far, PHF1 was found to be the 3′ partner in the JAZF1-PHF1 and EPC1-PHF1 chimeras but since the 6p21 rearrangements involve also other chromosomal translocation partners, other PHF1-fusions seem likely. Here, we show that PHF1 is recombined with a novel fusion partner, MEAF6 from 1p34, in an ESS carrying a t(1;6)(p34;p21) translocation as the sole karyotypic anomaly. 5′-RACE, RT-PCR, and sequencing showed the presence of an MEAF6-PHF1 chimera in the tumor with exon 5 of MEAF6 being fused in-frame to exon 2 of PHF1 so that the entire PHF1 coding region becomes the 3′ terminal part of the MEAF6-PHF1 fusion. The predicted fusion protein is composed of 750 amino acids and contains the histone acetyltransferase subunit NuA4 domain of MEAF6 and the tudor, PHD zinc finger, and MTF2 domains of PHF1. Although the specific functions of the MEAF6 and PHF1 proteins and why they are targeted by a neoplasia-specific gene fusion are not directly apparent, it seems that rearrangement of genes involved in acetylation (EPC1, MEAF6) and methylation (PHF1), resulting in aberrant gene expression, is a common theme in ESS pathogenesis.

Tedavi Almamış 221 Miyelodisplastik Sendromlu Hastada Sitogenetik Değerlendirme

Objective: Myelodysplastic syndromes (MDS) are a heterogeneous group of malignant clonal hematopoietic stem cell disorders characterized by bone marrow failure, ineffective hematopoiesis, peripheral blood cytopenias, atypic cytological profile, increased apoptosis, and increased likelihood of evolution to acute myeloid leukemia (AML). Cytogenetic findings are major determinants in the diagnosis, classification, pathogenesis, prognosis, and treatment in patients with MDS. Cytogenetic analysis is a mandatory step in the full evaluation of a newly diagnosed patient. The aim of the present study was to retrospectively evaluate the cytogenetic findings of 221 MDS patients in İstanbul University Cerrahpaşa Medical Faculty, Medical Biology and Genetics Department. Material and Methods: Cytogenetic analyses of 221 patients (89 female, 132 male) were performed on bone marrow cells using a trypsin-Giemsa banding technique. Metaphase cells were obtained from short-term unstimulated cultures. When possible, at least 20 metaphases were analyzed and 10 of them were fully karyotyped. Results: Among the 221 patients, 122 had no karyotype anomalies (55.20%) and 99 (44.80%) had clonal cytogenetic abnormalities; with 46 (20.81%) having one, 19 (8.59%) having two and 34 (15.38%) having complex (?3) abnormalities. According to the International Prognostic Scoring System (IPSS) cytogenetic categories, 130 (58.82%) patients presented with a good karyotype, 54 (24.44%) patients with intermediate karyotype and 37 (16.74%) patients with poor karyotype. Conclusion: Although some cases appear to have a normal karyotype, the technical failures such as inability to obtain sufficient analyzable metaphases may reduce the actual proportion of abnormal cases. The examination of 20 or more metaphases could further increase the sensitivity of cytogenetic analyses with clinical impact in individual cases by identifying additional abnormal clones or subclones.

Trisomy 8 in leukemia: A GCRI experience

Trisomy of chromosome 8 is frequently reported in myeloid lineage disorders and also detected in lymphoid neoplasms as well as solid tumors suggesting its role in neoplastic progression in general. It is likely to be a disease-modulating secondary event with underlying cryptic aberrations as it has been frequently reported in addition to known abnormalities contributing to clinical heterogeneity and modifying prognosis. Here, we share our findings of trisomy 8 in leukemia patients referred for diagnostic and prognostic cytogenetic assessment. Total 60 cases of trisomy 8, as a sole anomaly or in addition to other chromosomal aberrations, were reported (January 2005–September 2008). Unstimulated bone marrow or blood samples were cultured, followed by GTG banding and karyotyping as per the ISCN 2005. Patients with +8 were chronic myeloid leukemia (CML) (36), acute myeloid leukemia (AML) (17), and acute lymphoblastic leukemia (ALL) (7). In 7 patients, trisomy 8 was the sole anomaly, whereas in 6 patients +8 was in addition to normal clone, in 47 patients, the +8 was in addition to t(9;22), t(15;17), and others, including 3 with tetrasomy 8. Only one patient showed constitutional +8. The present study will form the basis of further cumulative studies to correlate potential differential effects of various karyotypic anomalies on disease progression and survival following a therapeutic regime. To unravel the role of extra 8 chromosome, constitutional chromosomal analysis and uniparental disomy will be considered.

Imaging clues in the prenatal diagnosis of syndromes and aneuploidy

Advances in fetal sonography and MRI have increased both the range and diagnostic accuracy of detectable fetal anomalies, with many anomalies detectable earlier in pregnancy. The presence of structural anomalies greatly raises the risk that the fetus has a syndrome or abnormal karyotype. In addition, new techniques in maternal serum screening have greatly increased the ability to identify pregnant patients at risk for anomalies and syndromes. This paper reviews maternal first- and second-trimester serum screening and imaging and covers many of the most common fetal karyotypic and structural anomalies.

Translocation t(11;17) Is Not Always Associated with Acute Myeloid or Acute Promyelocytic Leukemia

Abstract 5044Translocation t(11;17) is a rare chromosomal aberration that as an isolated entity is not pathognomonic of any hematologic disorder. Within the wide spectrum of chromosomal translocations, it is well recognized, though is uncommon, as a variant of acute promyelocytic leukemia (APL), with specific break-point at the PLZF gene on chromosome 11 forming a fusion gene the PLZF/RAR-α almost invariably resistant to all-trans retinoic acid (ATRA). Abnormal fusion of 11q23 mixed-lineage-leukemia (MLL) gene with the SEPT9 transcript on chromosome 17q25 in an acute monocytic (M5b) variant of acute myeloid leukemia (AML) is another example of an acute leukemia characterized by this chromosomal aberration. Sporadically, it has also been reported as a transient chromosomal break-point (q14;q12) in chronic myeloid leukemia (CML) (Olazábal et al. Cancer Genet Cytogenet. 2008). However, this chromosomal translocation is not well recognized in myelodysplastic syndrome (MDS) though nearly 50% of de novo and 80% of therapy-induced MDS (t-MDS) harbor karyotypic anomalies. In the present study, we report the natural history, clinical characteristics, outcome and the breakpoint regions in 2 patients with MDS and t(11;17) treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between 2000–2011. The first patient is an asymptomatic 28-year-old man presenting with a platelet count of 72,000/μL. The bone marrow morphology was consistent with a MDS, and clonal abnormality with karyotype 46, XY, t(11;17)(p11.2;p13) as a sole abnormality. Molecular analysis was negative for PML/RAR-α RNA transcript. The second patient is a 59-year-old woman who presented with mild fatigue, hemoglobin of 10.6 g/dL, platelet count of 84,000μ/L and was diagnosed with del(5q) MDS. Her bone marrow morphology was consistent with refractory cytopenia with multilineage dysplasia (RCMD) as defined by the World Health Organization (WHO),with an international prognostic scoring system (IPSS) intermediate-1 risk (score of 0.5). Her karyotype showed the translocation t(11;17) as a part of a clonal abnormality with karyotype 46,XX,del(5)(q13q33),t(11;17)(q24;q23). Both patients are being followed without treatment, as the peripheral blood counts are stable. The second patient is being considered for an allogeneic hematopoietic stem cell transplant (HSCT).These 2 patients are examples of non-APL/MLL-AML related translocation t(11;17) with different break-point regions. To our knowledge, there have only been several isolated cases of this translocation in patients with MDS. In this group of reported cases that included 4 women and 2 men (out of which 3 were children), the median age at presentation was 35; 2 cases were primary MDS while other 4 represented either t-MDS, MDS-derived AML, primary acute lymphoblastic leukemia (ALL) or AML. One of the previously reported patients with t(11;17)-related MDS was treated with a single course of decitabine, then subsequently underwent an unrelated-donor HSCT with an assumed favorable long-term outcome (Kreuziger et al. Leuk Res. 2007). Alternatively, the response to treatment in those of AML-M5b subtype and PLZF/RAR-α t(11;17)(q23;q11.12) was very poor (Tetsuya et al. Int J Hematol. 2008; Guidez et al. Leukemia. 1994).Thus, although the course of our 2 MDS patients associated with t(11;17) has been indolent to date, a larger cohort of patients and a longer follow-up is necessary before conclusions regarding prognosis and outcome can be made for this subgroup of patients with MDS. A review of the literature suggests these currently reported patients are the first with these particular break-point variations, and among the first altogether of adults with non-therapy related MDS with translocation t(11;17). Disclosures:No relevant conflicts of interest to declare.

Culture parameters for stable expansion, genetic modification and germline transmission of rat pluripotent stem cells.

SummaryThe ability of cultured pluripotent cells to contribute to the germline of chimaeric animals is essential to their utility for genetic manipulation. In the three years since rat embryonic stem (ES) cells were first reported the anticipated proliferation of genetically modified rat models from this new resource has not been realised. Culture instability, karyotypic anomalies, and strain variation are postulated to contribute to poor germline colonisation capacity. The resolution of these issues is essential to bring pluripotent cell-based genetic manipulation technology in the rat to the level of efficiency achieved in the mouse. Recent reports have described various alternative methods to maintain rat ES cells that include provision of additional small molecules and selective passaging methods. In contrast, we report that euploid, germline competent rat ES and embryonic germ (EG) cell lines can be maintained by simple adherent culture methods in defined medium supplemented with the original two inhibitors (2i) of the mitogen-activated protein kinase (ERK1/2) cascade and of glycogen synthase kinase 3, in combination with the cytokine leukaemia inhibitory factor (LIF). We demonstrate genetic modification, clonal expansion and transmission through the germline of rat ES and EG cell lines. We also describe a marked preference for full-term chimaera contribution when SD strain blastocysts are used as recipients for either DA or SD pluripotent stem cells.

Del(5q) in myeloid neoplasms

Note Interstitial del(5q) was first reported as a type of refractory anemia with characteristic clinical features; female predominance (unlike other MDS), macrocytosis, erythroid hypoplasia, frequent thrombocytosis and dysmegakaryopoiesis. It is one of the most common structural rearrangements in MDS (10%), seen as an isolated abnormality or with additional karyotypic anomalies. It is also observed in AML, with important prognostic significance.

Fetal gender ratio in recurrent miscarriages

Background:The purpose of this study was to evaluate the gender ratio and incidence of chromosomal anomalies in the products of conception (POC) from recurrent miscarriages.Methods:We determined the karyotypes of POC from patients with recurrent spontaneous miscarriages between 1999 and 2009.Results:In total, 313 specimens were successfully karyotyped, with a median gestational age of 10 weeks at miscarriage (interquartile range 8–13); 199 (64%) were females and 114 (36%) were males. In total, 121 (39%) had abnormal karyotypes, the most prevalent of which were chromosome 21 and 16 trisomies, triploidy, and monosomy X.Conclusion:Our findings suggest that female POC might be more susceptible to recurrent miscarriages than male ones during embryogenesis, implantation, and initial fetal development.

Focused microarray comparative genomic hybridisation compared to g-band karyotyping in a prospective prenatal population with a structural malformation identified on ultrasound scan

BackgroundArray comparative genomic hybridisation (aCGH) technology has allowed examination of the human genome at previously unthinkable resolution. It has enabled the detection of microdeletions and microduplications too small to be...

Síndrome de deleção 22q11 e cardiopatias congênitas complexas

OBJETIVO: Verificar a frequencia da sindrome de delecao 22q11 (SD22q11) entre pacientes portadores de cardiopatia congenita do tipo complexa. METODOS: A amostra foi constituida por uma coorte prospectiva e consecutiva de pacientes com cardiopatia complexa em sua primeira hospitalizacao em uma unidade de tratamento intensivo cardiologica de um hospital pediatrico. Para cada paciente foi preenchida uma ficha de avaliacao, com coleta de dados clinicos, e realizado o cariotipo de alta resolucao e tecnica de hibridizacao in situ fluorescente (FISH) com pesquisa de microdelecao 22q11. Os defeitos cardiacos foram classificados por um cardiologista participante do estudo. RESULTADOS: A amostra foi composta de 66 pacientes. Quanto a analise cariotipica, alteracoes foram observadas em cinco pacientes (7,6%); contudo, nenhum deles apresentava delecao 22q11. A avaliacao pela tecnica de FISH pode ser realizada com sucesso em 65 pacientes, sendo que a microdelecao 22q11 foi identificada em dois (3,1%). Dos 66 pacientes com defeitos complexos, 52 eram portadores de malformacoes do tipo conotruncal, sendo que em 51 a pesquisa para microdelecao 22q11 foi realizada. Os dois pacientes portadores da microdelecao 22q11 fizeram parte deste grupo, representando uma frequencia de 3,9%. Eles apresentavam tetralogia de Fallot. CONCLUSAO: A SD22q11 e uma anormalidade frequente entre pacientes com cardiopatias congenitas complexas e conotruncais. Variacoes da frequencia da SD22q11 entre os estudos parecem estar associadas, principalmente, com a forma adotada para a selecao da amostra e as caracteristicas da populacao em analise.

22q11.2 deletion syndrome and complex congenital heart defects

ObjectiveTo investigate the frequency of 22q11 deletion syndrome (22q11DS) in patients with complex congenital heart disease. MethodsA prospective and consecutive cohort of patients with complex heart defects was evaluated in their first hospitalization at a cardiac intensive care unit of a pediatric hospital. For each patient, an assessment form was completed with demographic information and clinical evaluation. High resolution karyotyping and fluorescence in situ hybridization (FISH) to detect the presence of 22q11 microdeletion, were performed. Heart defects were classified by a cardiologist. ResultsThe sample cohort consisted of 66 patients. Karyotypic anomalies were observed in 5 patients (7.6%); however, none of them had 22q11 deletion. Evaluation by FISH was successfully done in 65 patients, identifying 22q11 microdeletion in two patients (3.1%). Out of the 66 patients with complex defects, 52 were carriers of conotruncal malformations and in 51 patients, analysis for 22q11 microdeletion by FISH was performed. The two patients with 22q11 microdeletion belonged to this group, representing a frequency of 3.9%. They had tetralogy of Fallot. Conclusion22q11DS is a frequent abnormality among patients with complex and conotruncal heart defects. Variations of the 22q11DS frequency among studies seem to be mainly associated with criteria used for patient selection and specific characteristics of the population analyzed.

Clinical evaluation of the infertile male with respect to genetic etiologies

Severe male factor infertility may have a presently identifiable genetic basis. Y chromosomal microdeletions (e.g., an AZFc microdeletion), karyotypic anomalies (e.g., Klinefelter Syndrome), and mutations in both alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) gene may be found, depending upon the etiology of the reproductive compromise. Which patients should be tested, what are the tests that can be performed, when should those tests be ordered, and what might a positive outcome mean, are all critically valuable clinical questions for the couple that help guide evaluation and management. It is imperative that they be asked and results discussed prior to any intervention such as testis tissue extraction, microsurgical epididymal sperm aspiration, or intracytoplasmic sperm injection so that the couple can incorporate them in their decisions moving forward vis-à-vis their reproductive choices and options. The role of reproductive medicine clinicians should not be limited to just helping couples establish a pregnancy, but instead be expanded to educating them about the reasons and causes of their reproductive failure that affect not only them as individuals but also may have implications for their offspring.

Childhood intramuscular lipoma with a novel three way translocation. a case report

Lipomas are common benign adipocyte tumours of adults, and frequently exhibit clonality, with karyotypic anomalies occurring in approximately two-thirds of adult cases. In contrast, lipomas are exceptionally rare in childhood. We describe an intramuscular lipoma in the back of a healthy 5-year-old boy, with the initial MRI examination showing features suspicious of rhabdomyosarcoma. An incisional biopsy and a subsequent excisional biopsy were performed and both confirmed the lesion to be a lipoma. Cytoge-netic analysis demonstrated a three way translocation involving chromosomes 8q12, 17q25 and 13q14. The 8q11–13 breakpoints are common in lipoblastomas, but are rare in lipomas. It has been postulated that rearrangements involving this chromosomal breakpoint is associated with up-regulation of the PLAG1 gene. The 13q14 breakpoint is associated with a subset of lipomas, usually involving deletion of material from 13q with a minimal region of deletion identified in band 13q14. Our patient’s karyotype does not show a visible deletion, therefore a molecular technique would be required to investigate the possibility of submicroscopic deletion or rearrangement at this site. Lipomas in childhood are known to occur as part of the Bannayan-Riley-Ruvalcaba syndrome and Aicardi syndrome. Our patient is a normal, healthy 5-year-old child.

Does nuchal translucency thickness in the first trimester predict GDM onset during pregnancy?

Background and Aims. This study was planned to evaluate whether increased nuchal translucency (NT) thickness in the first trimester of gestation can be related to onset of gestational diabetes mellitus (GDM) during pregnancy.Methods. From January 2006 to August 2008, a group of 678 singleton pregnancies who had developed GDM has been selected as a study group among a total of 3966 pregnant women who had undergone first trimester screening for aneuploidies at 11–14 weeks of gestation. A group of 420 single pregnant women with physiological pregnancy were enrolled as control group. Both fetal structural and karyotype's anomalies were excluded in the two groups.NT was mesured by a Fetal Medicine Foundation certificated operator; GDM was diagnosed at 24–28 weeks of gestation following Carpenter and Coustan criteria. In the analyses of continuos variables, study and control group were compared by Student's t-test and Anova test.Results. There was no significative difference (p = 0.585) between NT values in the study (mean = 1.56) and control group (mean = 1.54).Conclusions. NT thickness does not show a significative increase in those women who subsequently develop GDM. Therefore, NT assessment does not prove to be an useful ultrasound parameter for predicting GDM onset during pregnancy.

Cytogenetic findings and reproductive outcome of infertile couples referred to an assisted reproduction program

It is still undefined whether all the couples entering an assisted reproduction program should undergo to karyotype analysis. The present study was conducted to determine the prevalence of chromosomal abnormalities in a non-selected sample of 1,146 couples referred to assisted reproduction technologies (ART), and to analyze the outcome of pregnancies from couples in whom cytogenetic anomalies were detected. Irrespective of the infertility factor, fertilization was achieved by intracytoplasmic sperm injection (ICSI). A total number of 35 karyotype anomalies were diagnosed, corresponding to an abnormality frequency of 1.52% (1.83% for men and 1.22% for women). As could be expected, the majority of men presenting katyotype anomalies had a low sperm count. Among women, the majority of cytogenetic anomalies were detected in individual not presenting risk factors for aberrant karyotype. Around 41% of pregnancies achieved in couples presenting chromosomal anomalies ended in spontaneous abortion. Information on fetal karyotype was limited. No major malformations were observed among newborns from parents with abnormal karyotype. In consideration of the elevated frequency of pregnancy loss, it seems advisable to recommend that chromosomal analysis be performed in all couples undergoing ART. This with the aim of identifying patients that would possibly benefit from pre-implantation genetic diagnosis.

Complex cytogenetic and molecular-genetic analysis of males with spermatogenesis failure

The chromosomal anomalies, microdeletions of AZF region of Y-chromosome and CFTR gene mutations have been studied among 80 infertile men with idiopathic spermatogenetic failure: 36 (45%) patients with aspermia, 19 (24%) patients with azoospermia and 25 (31%) patients with severe oligoasthenoteratozoospermia. In total 30% males with spermatogenetic failure genetic factor of infertility was observed. Karyotype anomalies were observed in 17.5% of infertile men, within 16.2% numerical and structural gonosomal anomalies and in 1.3%--Robertsonian translocation were revealed. In 11% males with spermatogenetic failure, Y-chromosome AZF region microdeletions were detected. The frequency of CFTR major mutation F508del among infertile men was 6.25%. 5T allele of polymorphic locus IVS8polyT was detected in 7.5% of examined men. The results obtained indicate the high complexity of cytogenetic and molecular-genetic studies of male infertility.

Early fetal growth: concepts and pitfalls

Early fetal growth: concepts and pitfalls