Cytogenetics Laboratory Research Articles

Heterogeneity of Stem Cells in Human Amniotic Fluid

Heterogeneity of Stem Cells in Human Amniotic Fluid Amniotic fluid contains a mixture of cells with capacity to differentiate into all germ layers. These cells are present in large numbers in midtrimester samples obtained for cytogenetic diagnosis, and have been identified by stem cell surface markers and transcription factors. We studied cultured samples from patients who had both direct cultures and matched cultures obtained 2 weeks later from the cytogenetics laboratory as well as patients with cytogenetics material only. Samples were cryogenically frozen, thawed, expanded in culture with excellent viability. There was considerable individual variation unrelated to gestational age or telomere length. Phenotype for embryonic markers was assessed by flow cytometry and by quantitative polymerase chain reaction. The most consistently present stem cell markers in substantial amounts were CD90, SSEA-4, & TRA-1-60. Cells with CD90, SSEA-4 & TRA-1-60 double and triple labeled also could be identified and subcultured, confirming the heterogeneity of the amniotic fluid stem cell population.

Heterogeneity of Stem Cells in Human Amniotic Fluid

Heterogeneity of Stem Cells in Human Amniotic Fluid Amniotic fluid contains a mixture of cells with capacity to differentiate into all germ layers. These cells are present in large numbers in midtrimester samples obtained for cytogenetic diagnosis, and have been identified by stem cell surface markers and transcription factors. We studied cultured samples from patients who had both direct cultures and matched cultures obtained 2 weeks later from the cytogenetics laboratory as well as patients with cytogenetics material only. Samples were cryogenically frozen, thawed, expanded in culture with excellent viability. There was considerable individual variation unrelated to gestational age or telomere length. Phenotype for embryonic markers was assessed by flow cytometry and by quantitative polymerase chain reaction. The most consistently present stem cell markers in substantial amounts were CD90, SSEA-4, & TRA-1-60. Cells with CD90, SSEA-4 & TRA-1-60 double and triple labeled also could be identified and subcultured, confirming the heterogeneity of the amniotic fluid stem cell population.

Antenatal cytogenetic testing in Havana, Cuba.

INTRODUCTION Antenatal cytogenetic testing was started in Havana in 1984, as a diagnostic option for fetal chromosome complement. The techniques applied are amniocyte culture, chorionic villus sampling, cordocentesis and fluorescence in situ hybridization in interphase cells. OBJECTIVE Describe the results of antenatal cytogenetic testing in the cytogenetic laboratory of the Cuba's National Medical Genetics Center in Havana, from 1984 through 2012. METHODS A retrospective descriptive study was carried out of the 22,928 pregnant women who had antenatal testing with conclusive results during the period 1984-2012. Information was obtained from laboratory databases for four antenatal diagnostic techniques. Variables studied were: antenatal diagnostic method, indications for genetic testing, type of chromosomal abnormality detected and couple's decision concerning pregnancy continuation if hereditary disease was diagnosed. Results were reported in absolute numbers and percentages. RESULTS Overall positivity was 2.8% (641 cases). Of the total, 20,565 samples were from amniocyte culture (558 positive cases, 2.7%); 1785 chorionic villus sampling (38 positive, 2.1%); 407 cord blood culture (28 positive, 6.9%); and 171 fluorescence in situ hybridization in interphase cells (17 positive, 9.9%). Advanced maternal age was the predominant indication for amniocyte culture and chorionic villus sampling. Positivity was higher for the two less frequently used methods, cordocentesis (6.9% positivity) and fluorescence in situ hybridization (9.9%). The predominant chromosomal abnormality was Down syndrome, with 45.4% of cases detected (291/641; 279 pure lines and 12 mosaic trisomies), followed by Edward syndrome with 12% (77/641, 71 pure lines and 6 mosaics) and Patau syndrome 4.7% (30/641, 27 pure lines and 3 mosaics). Sexual aneuploidy with pure lines affected 6.9% of cases (44/641) and with mosaicism 4.7% (30/641). Structural chromosomal abnormalities were detected in 22.5% of cases (144/641); of these, 70.8% (102/144) were balanced and 29.2% (42/144) unbalanced. In 78.6% of cases (504/641) with chromosomal abnormalities, whether mosaic or pure, the couple opted to terminate pregnancy. CONCLUSIONS Antenatal cytogenetic testing has helped reduce chromosomal abnormalities, mainly in Havana, and has provided reassurance of chromosomally normal children for couples at high genetic risk. The percentage of continuing pregnancies after a diagnosis of major chromosomal abnormality has been low, supporting evidence of broad population acceptance of abortion as an option when severe genetic abnormalities are present.

Mowat–Wilson syndrome associated with craniosynostosis

aDepartment of Clinical Genetics, Chapel Allerton Hospital bYorkshire Cytogenetics Laboratory, St James’ Hospital, Leeds, UK Correspondence to Verity L. Hartill, MBChB, Department of Clinical Genetics, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK Tel: +44 113 392 4432; fax: +44 113 392 4434; e-mail: [email protected] Received October 15, 2013 Accepted October 24, 2013

Modified cIg-FISH protocol for multiple myeloma in routine cytogenetic laboratory practice

The International Myeloma Working Group recommends that fluorescence in situ hybridization (FISH) be performed on specifically identified plasma cells (PC). This is because chromosomal abnormalities are not frequently detected by traditional karyotyping due to the low proliferative rate of PC in multiple myeloma (MM). Conventional FISH enhances the sensitivity but lacks the specificity, as it does not distinguish PC from other hematopoetic cells. To fulfill this recommendation, PC need to be selected either by flow cytometry or immunomagnetic bead-based PC sorting or by concomitant labeling of the cytoplasmic immunoglobulin light chain, which allows for unambiguous identification. These techniques require expertise, time, and funding and are not easily incorporated into the routine workflow of the cytogenetic laboratory. We have modified and refined the technique using fixed cell pellets to achieve nicely separated and easily identifiable PC. With immunostaining and subsequent FISH (i.e., cytoplasmic immunoglobulin FISH, cIg-FISH), this technique can be easily incorporated into every cytogenetic laboratory. Twenty samples from patients with MM were subjected to routine FISH, cIg-FISH, and chromosomal karyotyping and the results were compared. Three FISH probes, which enabled detection of the t(4;14), t(14;16) and deletion of TP53, were used to validate this modified technique successfully.

Diagnostic and Prognostic Significance Of Isolated Trisomy 2 In Hematopoietic Malignancies

Isolated trisomy 2 in hematopoietic malignancies is rare, having only been reported in eight cases in the literature. Of these cases, the majority are older male patients (7/8) ranging in age from 64 to 84 years. The underlying hematologic malignancies include: myelodysplastic syndrome (MDS), refractory anemia (RA) subtype; MDS, RA with excess blasts (RAEB-II) subtype; MDS, RAEB in transformation (RAEB-t); chronic myelomonocytic leukemia (CMML-t) in transformation; MDS transformed into AML; acute monoblastic and monocytic leukemia (AMoL; FAB M5); and AML in relapse. The molecular pathogenesis and prognostic significance of isolated trisomy 2 remains unknown due to the small number of reported cases. Herein, we report 11 cases of isolated trisomy 2 in hematologic disorders seen in the Mayo Clinic Cytogenetics laboratory from 1996-2012. The majority of patients were older males (7/11) ranging in age from 63 to 93 years. The underlying bone marrow pathologic diagnoses include: hypercellular bone marrow without diagnostic features of malignancy (cases 1 and 2); MDS, refractory cytopenia with multilineage dysplasia (RCMD) subtype (cases 3 and 4); RAEB-1 (cases 5 and 6); long-standing history of primary myelofibrosis now with 7% bone marrow blasts (case 7); acute myeloid leukemia (AML), not otherwise specified (cases 8 and 9); AML with myelodysplasia-related changes (cases 10 and 11). Trisomy 2 has been suggested to represent an age-related phenomenon as it is seen predominantly in older individuals demonstrating this abnormality. Our data suggests that this could be a possible explanation since all of the eleven cases were ages 63 and over. Based on the limited clinical information in our study, it appears that isolated trisomy 2 harbors little prognostic significance and that, rather, the prognostic significance is driven by the underlying pathologic diagnosis. For example, 3 of the 4 AML cases and the case of PMF with increasing bone marrow blasts survived only 7, 8, 6 weeks and 21 weeks post bone marrow biopsy/cytogenetic evaluation, respectively. Although our study only has two cases that lack diagnostic features of malignancy, one of these cases survived 10 years following the identification of the cytogenetic abnormality. Therefore, trisomy 2 as a sole abnormality should not be considered as definitive evidence for MDS in the absence of diagnostic morphological criteria (similar to trisomy 8 and 20q deletion). Disclosures:No relevant conflicts of interest to declare.

Subjectivity in chromosome band–level estimation: a multicenter study

Chromosome band level is the primary quality indicator for G-banded metaphase chromosome analysis. Although current professional guidelines address the minimum necessary band level for constitutional studies, there is no study documenting the comparative performance of different band-level estimation methods. This study compared 5 band-level estimation methods (Stallard, Vancouver, Welborn, United Kingdom External Quality Assurance Scheme, and Ford) in a multicenter study in which 82 readers from 7 different clinical cytogenetics laboratories evaluated the same 10 karyotypes (5 from amniotic fluid and 5 from peripheral blood) by each method. There was a 94% correlation between the five band-level estimation methods. The Welborn method yielded significantly lower scores for amniotic fluid karyotypes (P < 0.01) but not for peripheral blood karyotypes (P = 0.75). The distribution of scores obtained from different readers suggests a high level of subjectivity in chromosome band-level assessment. The variation in band-level estimation did not correlate with reader experience or study center, except for readers from one laboratory, for which the distribution of scores was significantly lower (P < 0.01). The results from this study suggest that the consistent use of one method is more important than the actual method employed for monitoring karyotype quality.

CHACO outreach project: the development of a primary health care-based medical genetic service in an Argentinean province

Dissemination of knowledge in genetics to be applied in medicine has created a growing need for capacity building in health care workers. The CAPABILITY ARGENTINA outreach project protocol was designed as a model to introduce genetics in areas without genetic services. Our aim was for genetic health care to become part of primary care in an Argentine province lacking genetic services. The program was innovative as professionals from the referral center (Garrahan Hospital S.A.M.I.C.) traveled to remote areas to train professionals through problem-based education. A logical framework was designed for a local needs assessment. Teaching materials (Powerpoint presentations, printed syllabus, and CD) and a web page were developed. A demonstration project was carried out in the Province of Chaco, Argentina. A total of 485 health workers were trained. The number of consultations increased significantly in participating areas comparing before and after the training period. To support this increase, a complementary project was set up from a public hospital sponsored from within Argentina to build a cytogenetic laboratory in the capital of the Province of Chaco. The model was improved for reproduction in other areas in Argentina. CAPABILITY ARGENTINA is a capacity building model for training of primary care professionals in genetics that may be applied to other medical specialties. The outcomes of the programme have a direct impact on clinical practice.

Pathogenic rare copy number variants in community-based schizophrenia suggest a potential role for clinical microarrays

Individually rare, large copy number variants (CNVs) contribute to genetic vulnerability for schizophrenia. Unresolved questions remain, however, regarding the anticipated yield of clinical microarray testing in schizophrenia. Using high-resolution genome-wide microarrays and rigorous methods, we investigated rare CNVs in a prospectively recruited community-based cohort of 459 unrelated adults with schizophrenia and estimated the minimum prevalence of clinically significant CNVs that would be detectable on a clinical microarray. A blinded review by two independent clinical cytogenetic laboratory directors of all large (>500 kb) rare CNVs in cases and well-matched controls showed that those deemed to be clinically significant were highly enriched in schizophrenia (16.4-fold increase, P < 0.0001). In a single community catchment area, the prevalence of individuals with these CNVs was 8.1%. Rare 1.7 Mb CNVs at 2q13 were found to be significantly associated with schizophrenia for the first time, compared with the prevalence in 23 838 population-based controls (42.9-fold increase, P = 0.0002). Additional novel findings that will facilitate the future clinical interpretation of smaller CNVs in schizophrenia include: (i) a greater proportion of individuals with two or more rare exonic CNVs >10 kb in size (1.5-fold increase, P = 0.0109) in schizophrenia; (ii) the systematic discovery of new candidate genes for schizophrenia; and, (iii) functional gene enrichment mapping highlighting a differential impact in schizophrenia of rare exonic deletions involving diverse functions, including neurodevelopmental and synaptic processes (4.7-fold increase, P = 0.0060). These findings suggest consideration of a potential role for clinical microarray testing in schizophrenia, as is now the suggested standard of care for related developmental disorders like autism.

Improving completeness of ascertainment and quality of information for pregnancies through linkage of administrative and clinical data records

PurposeBirth cohorts are a common tool used in epidemiological studies about pregnancy; yet these datasets systematically miss pregnancies that are spontaneously lost or terminated. This study examined the feasibility of linking administrative and clinical datasets from Alberta Canada to identify a pregnancy cohort that includes spontaneous and medical pregnancy losses. MethodsDeterministic linkage was used to link data from twelve clinical and administrative datasets for women who conceived between November 2007 and February 2008. Descriptive statistics were used to characterize the relative contribution of each dataset to the overall dataset. ResultsOverall, 6,477 unique pregnancies were eligible for inclusion, resulting in a live birth rate of 94.1%, a stillbirth rate of 0.5%, a fetal death rate of 4.1%, and an estimated 1.3% of the cohort moving out of the study area. No single dataset could identify all pregnancies. Individual databases identified 2.0–99.1% of the cohort. Fetal deaths were most frequently identified in outpatient physician claims, emergency room visits, ultrasound data, or from the cytogenetic laboratory. ConclusionsLinkage of clinical and administrative databases to identify pregnancy is feasible and can overcome many limitations associated with the use of a single dataset; however, fetal deaths continue to be under-ascertained.

CytoBayesJ: Software tools for Bayesian analysis of cytogenetic radiation dosimetry data

A number of authors have suggested that a Bayesian approach may be most appropriate for analysis of cytogenetic radiation dosimetry data. In the Bayesian framework, probability of an event is described in terms of previous expectations and uncertainty. Previously existing, or prior, information is used in combination with experimental results to infer probabilities or the likelihood that a hypothesis is true. It has been shown that the Bayesian approach increases both the accuracy and quality assurance of radiation dose estimates.New software entitled CytoBayesJ has been developed with the aim of bringing Bayesian analysis to cytogenetic biodosimetry laboratory practice. CytoBayesJ takes a number of Bayesian or ‘Bayesian like’ methods that have been proposed in the literature and presents them to the user in the form of simple user-friendly tools, including testing for the most appropriate model for distribution of chromosome aberrations and calculations of posterior probability distributions.The individual tools are described in detail and relevant examples of the use of the methods and the corresponding CytoBayesJ software tools are given. In this way, the suitability of the Bayesian approach to biological radiation dosimetry is highlighted and its wider application encouraged by providing a user-friendly software interface and manual in English and Russian.

Breast cancer evaluation and targeted investigational therapy (BEAT-IT): A pilot prospective tissue testing to guide clinical trial selection.

532 Background: An increasing number of molecularly targeted drugs are now available in Phase I and II clinical trials. Many of these drugs target specific molecular abnormalities such as mutated, amplified or rearranged genes. Our hypothesis is that cancers that carry a molecular abnormality that corresponds to the mechanism of action of a given investigational drug are more sensitive to that particular drug than other cancers. The objective of this study is to perform molecular analysis of metastatic breast cancer biopsies (bx) using methods already established within CLIA approved laboratories, and to use the results to triage pts to various therapeutic clinical trials or standard of care therapy. Methods: Four core needle biopsies (CNB) and 4 fine needle aspirations (FNA), or 8 FNA are obtained from the most safely accessible metastatic site in a single bx session. Pathological confirmation of successful aspiration is performed. Two core bx (or 4 FNA passes) are formaldehyde fixed and paraffin embedded for Immunohistochemistry (IHC), FISH and mutation analysis (CMS11 or CMS46) and 4 FNA are placed in RNA-later and snap-frozen for transcriptional profiles and storage. Samples are transferred to the Molecular Diagnostic, IHC, and Cytogenetics Laboratories. All reports are included in the electronic medical record. Results: FromFeb 2012 to Jan 2013, 142 pts referred, 128 pts registered, 101 bx completed and 78 (77%) bx with available results. Bx sites included: liver (37), lymph node (26), soft tissue (16), bone (13), lung (5), other (4). Successful results were obtained for IHC: PTEN (73%), AR (78%), MET (73%), FISH: EML4-ALK (78%) and MET (74%), and mutation analysis (76%). To date, there have been no reported hospitalizations, ER visits, bleeding, pain, infection or organ dysfunction at the bx sites. 16 pts have been treated on trials with investigational agents hypothesized to result in response based upon the molecular profile of the tumor. Conclusions: Prospective tissue collection to determine the molecular targets and to evaluate pts for clinical trial selection is feasible and safe.

QF‐PCR as a substitute for karyotyping of cytotrophoblast for the analysis of chorionic villi: advantages and limitations from a cytogenetic retrospective audit of 44,727 first‐trimester prenatal diagnoses

Karyotyping on chorionic villous samples (CVS) includes the analysis of both cytotrophoblast (STC) and mesenchyme (LTC). This approach requires complex laboratory organization and trained technicians. The introduction of quantitative fluorescent polymerase chain reaction (QF-PCR) instead of conventional karyotyping in low-risk pregnancies opened its application in CVS analysis. Discordant QF-PCR and CVS cytogenetic results were reported, and strategies for CVS analysis were introduced to minimize this risk. The possibility to substitute the STC with QF-PCR was reported. The aim of this study is to evaluate benefits and limitations of the approach QF-PCR + LTC compared with the traditional method STC + LTC and to quantify the associated risks of false results. This study is based on a retrospective cytogenetic audit of CVS results (n = 44 727) generated by the STC + LTC analytic approach. False-negative risks related to true fetal mosaicism type IV, imprinting syndromes and maternal contamination in LTC were calculated. Compared with STC + LTC, QF-PCR + LTC approach is associated with a cumulative false-negative risk of ~1/3100-1/4400. Costs and reporting time of STC in a high-throughput cytogenetic lab are similar to a CE-IVD marked QF-PCR analysis. These results should be clearly highlighted in the pre-test counseling and extensively discussed with the couple prior to testing for informed consent.

Impact of introducing a national policy for prenatal Down syndrome screening on the diagnostic invasive procedure rate in England

To evaluate the impact of the introduction of a Down syndrome screening policy in England, including implementation of the first-trimester combined screening test, on reducing prenatal invasive diagnostic procedure rates. All English cytogenetic laboratories were asked to submit data from the fiscal years 2003/2004 until 2011/2012 on all samples received from prenatal invasive procedures, including those that were undertaken following a higher-risk Down syndrome screening result. There was a gradual decline in the number of invasive procedures undertaken subsequent to a positive Down syndrome screening result in England, from 36 968 in 2003/2004 to 11 446 in 2008/2009, with only a relatively small subsequent decrease, to 10 215, in 2011/2012. This corresponds to a 72% reduction in the number of referrals received by the cytogenetic laboratories over a 9-year period and correlates with the national policy of implementing the combined screening test in place of second-trimester screening, which has reduced the overall screen-positive rate to 3.1% from an initial level of 6.0%. Implementation of a national Down syndrome screening policy based on the combined screening test has significantly reduced the number of invasive tests performed. However, as the combined screening test has become the replacement for second-trimester testing and has been almost completely implemented it appears that improvements in screening using current approaches may have reached their limits.

Diagnostic and clinical considerations in concomitant bone marrow involvement by plasma cell myeloma and chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis: a series of 15 cases and review of literature.

Plasma cell myeloma and chronic lymphocytic leukemia are both common hematologic malignancies, sharing many epidemiologic features. Concomitant detection of the 2 conditions poses special diagnostic challenges for the pathologist. To describe the pathologic findings in cases of concomitant bone marrow involvement by myeloma and CD5(+) monoclonal B cells and to outline the differential diagnostic possibilities, suggest a workup for correct diagnosis, and examine clinical outcome. Fifteen cases that met the diagnostic criteria were identified from pathology databases at 4 participating institutions. Morphologic findings were reviewed, additional immunohistochemical stains performed, and flow cytometric, cytogenetic, and relevant laboratory and clinical information was summarized. Previously published cases were searched from electronic databases and cross-references. Most patients (13 of 15) were older males. Often (11 of 15) they presented clinically with myeloma, yet had both monotypic plasma cells and B cells in the diagnostic marrow. In 4 patients, myeloma developed 24 months or later after chronic lymphocytic leukemia. In 7 patients, myeloma and CD5(+) B cells showed identical immunoglobulin light-chain restriction. Primary differential diagnoses include lymphoplasmacytic lymphoma, marginal zone lymphoma, and chronic lymphocytic leukemia with plasmacytoid differentiation. CD56 and/or cyclin D1 expression by plasma cells was helpful for correct diagnosis. Most patients in our cohort and published reports were treated for plasma cell myeloma. Concomitant detection of myeloma and chronic lymphocytic leukemia in the bone marrow is a rare event, which must be carefully differentiated from lymphomas with lymphoplasmacytic differentiation for correct treatment.

Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype

The 15q13.3 microdeletion syndrome (OMIM #612001) is characterized by a wide range of phenotypic features, including intellectual disability, seizures, autism, and psychiatric conditions. This deletion is inherited in approximately 75% of cases and has been found in mildly affected and normal parents, consistent with variable expressivity and incomplete penetrance. The common deletion is approximately 2 Mb and contains several genes; however, the gene(s) responsible for the resulting clinical features have not been clearly defined. Recently, four probands were reported with small deletions including only the CHRNA7 gene. These patients showed a wide range of phenotypic features similar to those associated with the larger 15q13.3 microdeletion. To further correlate genotype and phenotype, we queried our database of >15,000 patients tested in the Mayo Clinic Cytogenetics Laboratory from 2008 to 2011 and identified 19 individuals (10 probands and 9 family members) with isolated heterozygous CHRNA7 gene deletions. All but two infants displayed multiple features consistent with 15q13.3 microdeletion syndrome. We also identified the first de novo deletion confined to CHRNA7 as well as the second known case with homozygous deletion of CHRNA7 only. These results provide further evidence implicating CHRNA7 as the gene responsible for the clinical findings associated with 15q13.3 microdeletion.

A parallel study of different array-CGH platforms in a set of Spanish patients with developmental delay and intellectual disability

Developmental delay and intellectual disability, which occur in 1–3% of the population, account for a large number of the cases regularly seen in genetic units. Chromosomal microarray analysis has been shown to be a valuable clinical diagnostic assay and it should be the first-tier clinical diagnostic test for individuals with these conditions. However and due to several difficulties such as the platform resolution, the cost, and the inexperience with genomic data bases, the implementation of this test in many cytogenetic laboratories has been delayed. In an attempt to provide more insights of the benefits derived by using the chromosomal microarray analysis, this study presents the experience of two clinical centers using three different microarray platforms. The results obtained using a custom microarray (KaryoArray®) and two different commercial medium- and high-resolution whole-genome oligonucleotide microarrays have been compared. An overall diagnostic yield of around 15% has been obtained. However, the custom microarray platform has been shown to be more convenient for a clinical setting, since it allows the detection of more pathogenic copy number variants and less common variants.

PREDICTORS OF PRENATAL SCREENING IN A LOW-SCREENING POPULATION

IntroductionNew prenatal screening technologies have made it possible for a simple blood test to assist in the identification of several conditions in the fetus early in pregnancy. Given more information...

Electronic Clinical Laboratory Reports as a Source for Ascertaining and Confirming Chromosomal Anomalies Reported to the New York State Congenital Malformations Registry

Hospitals and physicians are required to submit case reports with confirmatory diagnosis information to the New York State Congenital Malformations Registry (CMR) on children who are born or reside in New York State and are diagnosed with major birth defects. However, the majority of the cases with chromosomal anomalies indicated in the hospital discharge files are reported to the CMR without confirmatory testing data, which are usually not available at the time of reporting. To link the cytogenetic test reports, submitted by cytogenetic testing laboratories via Electronic Clinical Laboratory Reporting System (ECLRS), to the CMR cases in order to obtain confirmatory diagnoses and identify unreported cases with chromosomal anomalies. : Cytogenetic testing data, submitted by the New York State licensed laboratories, that are stored on the ECLRS Sybase server were retrieved and matched to the CMR cases. The laboratory testing results were used to confirm diagnoses of the CMR cases for matched reports and to ascertain new birth defects cases by auditing hospitals and physicians using unmatched reports with abnormal testing results. By the end of 2010, a total of 927 reports on 747 children were submitted to the CMR by 14 cytogenetic testing laboratories via the New York State Department of Health ECLRS. Among the 747 children reported, 398 children (53%) had abnormal test results and 412 children (55%) were matched to the CMR cases. From these laboratory reports, 151 new cases with chromosomal anomalies were identified, confirmed, and were added to the CMR. The additional cases accounted for about 7.8% of all cases with chromosomal anomalies in the CMR for the reporting years 2008-2010. Cytogenetic laboratory reports can serve as an important source for ascertaining and confirming chromosomal anomalies. Acquiring molecular genetics testing data directly from cytogenetic testing laboratories via ECLRS enables CMR staff to confirm diagnoses and improve the accuracy and efficiency of case reporting.

10. kromozomdaki perisentrik inversiyonun agresif davranış ve hiperaktivite üzerine etkisi

Aggressive behavior and hyperactivity are neurodevelopmental diseases with unknown pathogenesis. Pericentric inv(10)(p11.2;q21.2) mutation is frequently encountered in cytogenetic laboratories. This mutation is accepted as a polymorphic variant and is phenotypically silent, but in some cases it has been associated with neurodevelopmental diseases like autism. After blood culturing, standard chromosome obtaining procedure was applied to patients. In this study, clinical and cytogenetical findings of a boy with developmental delay, mental and motor retardation, attention deficit and hyperactivity have been reported. As a result of chromosome analysis, on chromosome 10, a large pericentric inversion between p11.1 and q22.q bands has been found. Karyotype analysis was also performed to mother, father and siblings of the patient and they have been found to have normal karyotype. It is plausible to consider a relation between inv(10) and some behavioral problems. Additionally, molecular studies targeting 10p-q critical region will be more informative for the true identification of this disease.