77 results on '"Rivka Sukenik-Halevy"'
Search Results
2. P792: Amniotic fluid fetal DNA concentration is higher in females and varies with gestational age
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Yoel Gofin, Ran Svirsky, Dana Lavi Ben Atav, Meytal Liberman, Tamar Tenne, and Rivka Sukenik-Halevy
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Genetics ,QH426-470 ,Medicine - Published
- 2024
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3. Prenatal gender-customized head circumference nomograms result in reclassification of microcephaly and macrocephalyAJOG Global Reports at a Glance
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Rivka Sukenik-Halevy, MD, Ella Golbary Kinory, MS, Tamar Laron Kenet, MD, Dana Brabbing-Goldstein, MD, Yinon Gilboa, MD, Lina Basel-Salmon, MD, PhD, and Sharon Perlman, MD
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curve ,head circumference ,gender customized ,Gynecology and obstetrics ,RG1-991 - Abstract
BACKGROUND: Local and worldwide prenatal charts for estimated fetal weight and postnatal charts for head circumference are gender specific. However, prenatal head circumference nomograms are not gender customized. OBJECTIVE: This study aimed to create gender-customized curves to assess between-gender head circumference differences and to study the clinical significance of using such gender-customized curves. STUDY DESIGN: A single-center retrospective study was conducted between June 2012 and December 2020. Prenatal head circumference measurements were obtained from routine estimated fetal weight ultrasound scans. Postnatal head circumference measurement at birth and gender were retrieved from computerized neonatal files. Head circumference curves were created, and the normal range was defined for the male and female subpopulations. After applying gender-specific curves, we analyzed the outcome of cases classified as microcephaly and macrocephaly according to non–gender-customized curves, which were reclassified as normal according to gender-specific curves. For these cases, clinical information and postnatal long-term outcomes were retrieved from patients’ medical records. RESULTS: The cohort included 11,404 participants (6000 males and 5404 females). The curve for male head circumference was significantly higher than the female curve for all gestational weeks (P
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- 2023
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4. Expanding the phenotype of familial hypocalciuric hypercalcemia type 3: Case report and review of the literature
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Lior Baraf, Noa Shefer Averbuch, Lior Carmon, Auryan Szalat, Rivka Sukenik-Halevy, and Merav Fraenkel
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FHH3 ,Pancreatitis ,AP2S1 ,Hypercalcemia ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background: Familial hypocalciuric hypercalcemia (FHH) is a rare condition that affects the calcium sensing receptor and its associated proteins, causing parathyroid hormone (PTH)-mediated hypercalcemia. FHH is inherited in an autosomal dominant pattern. Most persons with FHH are asymptomatic. Case presentation: A 30-year-old Caucasian male was sent for evaluation to our endocrinology unit due to recurrent pancreatitis in the context of chronic hypercalcemia, and a biochemical profile compatible with FHH. Genetic evaluation did not show any mutations associated with pancreatitis but revealed a known heterozygous variant in the AP2S1 gene: c.44G > T, p.Arg15Leu, responsible for FHH type 3 (FHH3). A bone mineral density DXA scan detected low bone mass, in the osteoporotic range, with no other secondary causes. Both his parents were normocalcemic. Treatment with the calcimimetic cinacalcet normalized his blood calcium; no episodes of pancreatitis have occurred during 26 months follow up. The patient's only child was found to have hypercalcemia at age three years. His lab results were compatible with the diagnosis of FHH, and he was found to carry the same AP2S1 gene mutation as his father. His calcium level was elevated but he did not have any symptoms related to hypercalcemia. He was diagnosed with speech delay. Conclusions: We describe a man with a de-novo mutation leading to FHH3, who presented with a rare combination of symptoms, including recurrent pancreatitis and low bone mass, whereas his child presented with speech delay. Hypercalcemia and related FHH3 morbidities may respond to calcimimetics.
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- 2022
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5. Large scale population screening for Duchenne muscular dystrophy—Predictable and unpredictable challenges
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Gal Cohen, Atalia Shtorch‐Asor, Shay Ben‐Shachar, Racheli Goldfarb‐Yaacobi, Meirav Kaiser, Revital Rosenfeld, Mika Vinovezky, Dana Irge, Yael Furman, Dafni Reiss, Shira Litz‐Philipsborn, and Rivka Sukenik‐Halevy
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Dystrophin ,Muscular Dystrophy, Duchenne ,Mutation ,Humans ,Obstetrics and Gynecology ,Female ,Exons ,Multiplex Polymerase Chain Reaction ,Gene Deletion ,Genetics (clinical) - Abstract
Large deletions and duplications account for 65%-80% of pathogenic Duchenne muscular dystrophy (DMD) variants. A nationwide carrier screening for DMD was initiated in Israel in 2020. We assessed the carrier rate and spectrum of variants detected in a cohort of women screened for DMD carrier status and analyzed screening efficacy and challenges related to DMD population screening.A cohort of 12,362 women were tested at a single institute using multiplex ligation-dependent probe amplification based copy number analysis of the 79 DMD exons. Consecutive sequencing of the primer region was performed when a single exon deletion was suspected.Deletions involving multiple exons were detected in seven cases and duplications involving multiple exons were found in four. Of these, nine were pathogenic based on previous reports and familial segregation testing, translating to a carrier rate of 1:1374. A family history was reported in three cases. Single exon deletions were suspected in 81 cases; further sequencing detected a single nucleotide variant affecting probe hybridization. These cases clustered according to ethnic origin.Population screening for DMD has a significant yield. Most carriers did not report a family history of dystrophinopathies. Screening should be adjusted for methodological limitations. Some cases may require extensive genetic counseling and work-up.
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- 2022
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6. A call for public funding of invasive and non-invasive prenatal testing
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Idit Maya, Rivka Sukenik-Halevy, Lina Basel-Salmon, and Lena Sagi-Dain
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Pediatrics, Perinatology and Child Health ,Obstetrics and Gynecology - Abstract
For decades, prenatal screening and genetic testing strategies were limited, requiring less complex decisions. Recently, however, several new advanced technologies were introduced, including chromosomal microarray analysis (CMA) and non-invasive prenatal screening (NIPS), bringing about the need to choose the most appropriate testing for each pregnancy. A worrisome issue is that opposed to the wide implementation and debates over public funding of NIPS, currently invasive testing is still recommended only in selected pregnancies with increased risk for chromosomal aberrations (according to screening tests or sonographic anomalies). This current decision-making regarding public funding for invasive and screening testing might compromise informed consent and patient’s autonomy. In this manuscript, we compare several characteristics of CMA vs. NIPS, namely: the accuracy and the diagnostic scope, the risks for miscarriage and for clinically uncertain findings, the timing for testing, and pretest counselling. We argue that it must be recognized that one size might not fit all, and suggest that both options should be presented to all couples through early genetic counseling, with public funding for the specific selected test.
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- 2023
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7. Possible biallelic inheritance in TIE1 in a family with congenital lymphedema, intestinal lymphangiectasia and cutis aplasia
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Aasem Abu Shtaya, Rivka Sukenik‐Halevy, Lily Bazak, Gabriel Arie Lidzbarsky, Claudia Gonzaga‐Jauregui, Irina Lagovsky, Yael Goldberg, and Lina Basel‐Salmon
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Genetics ,Genetics (clinical) - Published
- 2023
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8. The prevalence of prenatal sonographic findings in postnatal diagnostic exome sequencing performed for neurocognitive phenotypes: A cohort study
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Rivka, Sukenik-Halevy, Sharon, Perlman, Noa, Ruhrman-Shahar, Offra, Engel, Naama, Orenstein, Claudia, Gonzaga-Jauregui, Alan R, Shuldiner, Nurit, Magal, Ofir, Hagari, Noy, Azulay, Gabriel Arie, Lidzbarsky, Lily, Bazak, and Lina, Basel-Salmon
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Cohort Studies ,Polyhydramnios ,Fetal Growth Retardation ,Phenotype ,Pregnancy ,Prenatal Diagnosis ,Prevalence ,Humans ,Obstetrics and Gynecology ,Exome ,Female ,Ultrasonography, Prenatal ,Genetics (clinical) - Abstract
Prenatal exome sequencing (ES) is currently indicated for fetal malformations. Some neurocognitive genetic disorders may not have a prenatal phenotype. We assessed the prevalence of prenatally detectable phenotypes among patients with neurocognitive syndromes diagnosed postnatally by ES.The medical files of a cohort of 138 patients diagnosed postnatally with a neurocognitive disorder using ES were reviewed for prenatal sonographic data. The Online Mendelian Inheritance in Man (OMIM) database was searched for prenatally detectable phenotypes for all genes identified.Prenatal imaging data were available for 122 cases. Of these, 29 (23.75%) had fetal structural abnormalities and another 29 had other ultrasound abnormalities (fetal growth restriction, polyhydramnios, elevated nuchal translucency). In 30 patients, structural aberrations that were not diagnosed prenatally were detected at birth; in 21 (17.2%), the abnormalities could theoretically be detected prenatally by third-trimester/targeted scans. According to OMIM, 55.9% of the diagnosed genes were not associated with structural anomalies.Most patients (52.5%) with postnatally diagnosed neurocognitive disorders did not have prenatal sonographic findings indicating prenatal ES should be considered. The prevalence of specific prenatal phenotypes such as fetal growth restriction and polyhydramnios in our cohort suggests that additional prenatal findings should be assessed as possible indications for prenatal ES.
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- 2022
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9. The diagnostic efficacy of exome data analysis using fixed neurodevelopmental gene lists: Implications for prenatal setting
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Rivka Sukenik-Halevy, Noa Ruhrman-Shahar, Lina Basel-Salmon, Noy Azulay, Alan R. Shuldiner, Claudia Gonzaga-Jauregui, Ofir Hagari, Lily Bazak, Nurit Magal, Gabriel Arie Lidzbarsky, and Naama Orenstein
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0301 basic medicine ,Proband ,Pediatrics ,medicine.medical_specialty ,Noninvasive Prenatal Testing ,MEDLINE ,Prenatal diagnosis ,030105 genetics & heredity ,03 medical and health sciences ,Fetus ,0302 clinical medicine ,Pregnancy ,Exome Sequencing ,Humans ,Medicine ,Exome ,Genetics (clinical) ,Exome sequencing ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics and Gynecology ,Cohort ,Female ,business ,Neurocognitive - Abstract
Objective Laboratories performing prenatal exome sequencing (ES) frequently limit analysis to predetermined gene lists. We used a diagnostic postnatal ES cohort to assess how many of the genes diagnosed are not included in a number of select fixed lists used for prenatal diagnosis. Methods Of 601 postnatal ES tests, pathogenic variants related to neurodevelopmental disorders were detected in 138 probands. We evaluated if causative genes were present in the following: (1) Developmental Disorders Genotype-Phenotype database list, (2) a commercial laboratory list for prenatal ES, (3) the PanelApp fetal anomalies panel, and (4) a published list used for prenatal diagnosis by ES (Prenatal Assessment of Genomes and Exomes study). Results The percentages of cases where the diagnosed gene was not included in the selected four lists were; 11.6%, 17.24%, 23.2%, and 10.9%, respectively. In 13/138 (9.4%) cases, the causative gene was not included in any of the lists; in 4/13 (∼30%) cases noninclusion was explained by a relatively recent discovery of gene-phenotype association. Conclusions A significant number of genes related to neurocognitive phenotypes are not included in some of the lists used for prenatal ES data interpretation. These are not only genes related to recently discovered disorders, but also genes with well-established gene-phenotype.
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- 2021
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10. When phenotype does not match genotype: importance of 'real-time' refining of phenotypic information for exome data interpretation
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Yael Goldberg, Noa Ruhrman-Shahar, Rivka Sukenik-Halevy, Noy Azulay, Idit Maya, Alan R. Shuldiner, Claudia Gonzaga-Jauregui, Lina Basel-Salmon, Ofir Hagari, Nurit Magal, Lily Bazak, Naama Orenstein, and Gabriel Arie Lidzbarsky
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Proband ,Genetics ,medicine.diagnostic_test ,Cosegregation ,Genetic counseling ,Genotype ,medicine ,Biology ,Phenotype ,Exome ,Genetics (clinical) ,Exome sequencing ,Genetic testing - Abstract
PURPOSE Clinical data provided to genetic testing laboratories are frequently scarce. Our purpose was to evaluate clinical scenarios where phenotypic refinement in proband's family members might impact exome data interpretation. METHODS Of 614 exomes, 209 were diagnostic and included in this study. Phenotypic information was gathered by the variant interpretation team from genetic counseling letters and images. If a discrepancy between reported clinical findings and presumably disease-causing variant segregation was observed, referring clinicians were contacted for phenotypic clarification. RESULTS In 16/209 (7.7%) cases, phenotypic refinement was important due to (1) lack of cosegregation of disease-causing variant with the reported phenotype; (2) identification of different disorders with overlapping symptoms in the same family; (3) similar features in proband and family members, but molecular cause identified in proband only; and (4) previously unrecognized maternal condition causative of child's phenotype. As a result of phenotypic clarification, in 12/16 (75%) cases definition of affected versus unaffected status in one of the family members has changed, and in one case variant classification has changed. CONCLUSION Detailed description of phenotypes in family members including differences in clinical presentations, even if subtle, are important in exome interpretation and should be communicated to the variant interpretation team.
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- 2021
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11. Teaching clinicians practical genomic medicine: 7 years’ experience in a tertiary care center
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Naama Oresntein, Arie Koifman, Efrat Sofrin-Drucker, Adi Reches, Noa Rhurman-Shahar, Gal Zaks-Hoffer, Nurit Magal, Doron M. Behar, Yael Goldberg, Daphna Marom, Mordechai Shohat, Lina Basel-Salmon, Noa Shefer Averbuch, Lily Bazak, Reut Matar, Sagi Josefberg, Nesia Kropach-Gilad, Rachel Michaelson-Cohen, Rivka Sukenik-Halevy, Avi Fellner, Liat Salzer-Sheelo, Monika Weiss-Hubshmann, and Idit Maya
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medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Tertiary care ,Literacy ,Clinical Practice ,Knowledge change ,Family medicine ,Program completion ,Medicine ,Genomic medicine ,business ,Genetics (clinical) ,media_common - Abstract
Increased implementation of complex genetic technologies in clinical practice emphasizes the urgency of genomic literacy and proficiency for medical professionals. We evaluated our genomic education model. We assessed the 5-day, extended format program, encompassing lectures, videos, interactive tests, practice cases, and clinical exercises. Pre- and post questionnaires assessed knowledge change, using t-tests to compare groups. Satisfaction on program completion and after 3 years were evaluated. Implementation in other centers determined acceptability. During 2012–2018, 774 clinicians from multiple disciplines and career stages attended 35 programs; 334 (43%) attended the 5-day extended format. Evaluations showed significant improvement of genomic literacy (mean 15.05/100 points, p
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- 2020
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12. Chromosomal microarray should be performed for cases of fetal short long bones detected prenatally
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Amihood Singer, Morad Khayat, Rachel Michaelson-Cohen, Hagit Daum, Lena Sagi-Dain, Keren Tzadikevitch Geffen, Shay Ben-Shachar, Rivka Sukenik Halevy, Michal Feingold-Zadok, and Idit Maya
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Short long bone ,medicine.medical_specialty ,Percentile ,Fetus ,030219 obstetrics & reproductive medicine ,Microarray ,business.industry ,Obstetrics ,Obstetrics and Gynecology ,General Medicine ,Bone length ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Cohort ,Medicine ,Copy-number variation ,business ,Likely pathogenic - Abstract
To investigate the prevalence of pathogenic and likely-pathogenic variants detected by chromosomal microarray analysis (CMA), among pregnancies with fetal short long bones diagnosed by ultrasound. The study cohort was based on cases of chromosomal microarray analyses performed nationwide for the indication of short long bones. CMA was performed in 66 cases of short long bones. There were 4 cases with a pathogenic/likely pathogenic result (6%). The rate of chromosomal abnormalities was significantly higher compared to the background risk for copy number variations (CNVs) in pregnancies with no sonographic anomalies (P
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- 2020
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13. The yield of chromosomal microarray testing for cases of abnormal fetal head circumference
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Morad Khayat, Yael Pasternak, Rivka Sukenik Halevy, Sharon Zeligson, Shay Ben-Shachar, Amihood Singer, Lena Sagi-Dain, Michal Feingold-Zadok, Lior Greenbaum, and Idit Maya
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Microcephaly ,DNA Copy Number Variations ,Genetic counseling ,030105 genetics & heredity ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Humans ,Medicine ,Fetal head ,Retrospective Studies ,Fetus ,business.industry ,Obstetrics ,Medical record ,Macrocephaly ,Obstetrics and Gynecology ,Microarray Analysis ,medicine.disease ,Megalencephaly ,Cytogenetic Analysis ,Pediatrics, Perinatology and Child Health ,Cohort ,Amniocentesis ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Objectives Chromosomal microarray analysis (CMA) is the method of choice for genetic work-up in cases of fetal malformations. We assessed the detection rate of CMA in cases of abnormal fetal head circumference (HC). Methods The study cohort was based on 81 cases of amniocenteses performed throughout Israel for the indication of microcephaly (53) or macrocephaly (28), from January 2015 through December 2018. We retrieved data regarding the clinical background, parental HCs and work-up during the pregnancy from genetic counseling summaries and from patients’ medical records. Results There was only one likely pathogenic CMA result (1.89%): a 400-kb microdeletion at 16p13.3 detected in a case of isolated microcephaly. No pathogenic results were found in the macrocephaly group. Most fetuses with microcephaly were female (87.8%), while the majority with macrocephaly were males (86.4%). Conclusions The results imply that CMA analysis in pregnancies with microcephaly may carry a small yield compared to other indications. Regarding macrocephaly, our cohort was too small to draw conclusions. In light of the significant gender effect on the diagnosis of abnormal HC, standardization of fetal HC charts according to fetal gender may normalize cases that were categorized outside the normal range and may increase the yield of CMA for cases of abnormal HC.
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- 2020
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14. Characterization of functional transposable element enhancers in acute myeloid leukemia
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Yingying Zeng, Denghui Liu, Yaqiang Cao, Rivka Sukenik Halevy, Nadav Ahituv, Picard Nguyen, Xiaoli Zhang, and Jing-Dong J. Han
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0301 basic medicine ,Myeloid ,Carcinogenesis ,Biology ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,Epigenetics ,Nucleotide Motifs ,Enhancer ,neoplasms ,Gene ,General Environmental Science ,Gene Expression Regulation, Leukemic ,Genome, Human ,Myeloid leukemia ,Chromatin ,Leukemia, Myeloid, Acute ,Haematopoiesis ,Enhancer Elements, Genetic ,Gene Ontology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,DNA Transposable Elements ,Cancer research ,General Agricultural and Biological Sciences ,Transcription Factors ,K562 cells - Abstract
Transposable elements (TEs) have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes. Acute myeloid leukemia (AML) develops as a consequence of a series of genetic changes in hematopoietic precursor cells, including mutations in epigenetic factors. Here, we set out to study the gene regulatory role of TEs in AML. We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data. We show that a large number of TEs in general, and more specifically mammalian-wide interspersed repeats (MIRs), are more enriched in AML cells than in normal blood cells. We obtained a similar finding when analyzing histone modification data in AML patients. Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis. To functionally validate their regulatory role, we selected 19 MIR regions in AML cells, and tested them for enhancer activity in an AML cell line (Kasumi-1) and a chronic myeloid leukemia (CML) cell line (K562); the results revealed several MIRs to be functional enhancers. Taken together, our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.
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- 2020
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15. Expanding the phenotype of Familial hypocalciuric hypercalcemia type 3
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Lior Baraf, Noa Averbuch, Lior Carmon, Auryan Szalat, Rivka Sukenik-Halevy, and Merav Fraenkel
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- 2022
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16. Does parity affect pregnancy outcomes in the elderly gravida?
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Rivka Sukenik Halevy, Tal Biron-Shental, Ofer Markovitch, Dana Sadeh-Mestechkin, Yael Ganor Paz, and Gil Shechter-Maor
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Pregnancy ,medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,Obstetrics ,business.industry ,Medical record ,Obstetrics and Gynecology ,Retrospective cohort study ,General Medicine ,medicine.disease ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Cohort ,medicine ,Medical history ,Advanced maternal age ,business ,Twin Pregnancy - Abstract
To identify whether older primiparas have more complications than do women who continue to deliver children into their late reproductive age. Patients of at least 35 years of age at delivery were included. Within this cohort, data from primiparous and multiparous women were compared. This retrospective study was based on electronic medical records from a single academic center, with more than 7000 deliveries annually. The impact of parity on maternal complications was assessed using a multivariate logistic regression model that adjusted for baseline maternal characteristics and medical history. During the study period, there were 54 283 deliveries in our medical center. A total of 13,982 (25.7%) patients were at least 35 years old at delivery. The rate of twin pregnancy was higher in the primiparous group (1.9%) as compared to the multiparous group (0.8%, 95% CI 0.30–0.64, P
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- 2019
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17. A new method for evaluating short fetal corpus callosum
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Ronnie Tepper, Zvi Leibovitz, Rivka Sukenik-Halevy, and Catherine Garel
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Adult ,0301 basic medicine ,030105 genetics & heredity ,Corpus callosum ,Ultrasonography, Prenatal ,Corpus Callosum ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Humans ,Medicine ,Genetics (clinical) ,Retrospective Studies ,Fetus ,030219 obstetrics & reproductive medicine ,Cephalic index ,business.industry ,Obstetrics and Gynecology ,Gestational age ,Fetal Presentation ,medicine.disease ,Sagittal plane ,medicine.anatomical_structure ,Gestation ,Female ,Agenesis of Corpus Callosum ,Nuclear medicine ,business - Abstract
OBJECTIVE Sonographic diagnosis of short corpus callosum (SCC) is based on measurement of a short for gestational age antero-posterior length of the corpus callosum (CC) in the midsagittal plane. We suggest a new method for evaluating SCC without referring to biometry tables. METHODS We measured the ratio between the CC length and the internal cranial occipitofrontal dimension (ICOFD) in the midsagittal plane in 399 normal fetuses at 20 + 6 to 35 + 3 weeks of gestation and in 31 fetuses with a diagnosis of a SCC and compared the mean ratio between two groups. The impact of cephalic biometric parameters, fetal presentation, and gender was assessed. RESULTS The ICOFD/CC length for normal pregnancies was constant throughout the pregnancy (2.35 ± 0.11). There was no correlation between the ICOFD/CC length and cephalic index, Biparietal Diameter (BPD), head circumference, fetal sex, or fetal presentation. The ratio of pregnancies with SCC was significantly higher: 3.20 ± 0.84 (P < .0001). CONCLUSION The ICOFD/CC length practically does not change throughout a normal pregnancy. The ratio was significantly higher in pregnancies with SCC. Measuring this ratio during fetal anatomical scan may enable rapid evaluation of the CC without the need to refer to biometry tables.
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- 2019
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18. A Rare Case of 7 Simultaneous Arterial Dissections and Review of The Literature
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Daphna Amitai Komem, Yair Levy, Ali Shnaker, Jonathan Weissmann, Rivka Sukenik Halevy, Simone Fajer, and Yigal Griton
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medicine.medical_specialty ,Computed Tomography Angiography ,Dissection (medical) ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Pseudoaneurysm ,0302 clinical medicine ,Risk Factors ,Rare case ,Humans ,Medicine ,Genetic Predisposition to Disease ,Artery dissection ,Arterial dissection ,business.industry ,Endovascular Procedures ,030208 emergency & critical care medicine ,General Medicine ,Middle Aged ,medicine.disease ,Aortic Dissection ,Viscera ,Collagen Type III ,Phenotype ,Treatment Outcome ,Iliac Aneurysm ,Mutation ,Female ,Surgery ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Carotid Artery, Internal - Abstract
Objective: Spontaneous multiple artery dissection is a relatively rare phenomenon. Early clinical signs are often nonspecific, making it difficult to diagnose. Case Report: This is a case of a 51-year-old female who presented with spontaneous dissection of 4 visceral arteries, both iliac arteries, and of the right internal carotid artery. The patient underwent urgent successful endovascular repair. Later complications included acute respiratory distress syndrome and pneumonia after massive blood transfusion. She recovered gradually and was discharged after 21 days. Due to this rare presentation, genetic investigation was performed in search of a connective tissue disorder. Results revealed a new COL3A1 subtype mutation. The pathogenicity of this variant remains unclear. Conclusion: We recommend a high index of suspicion for visceral artery dissection in the differential diagnosis for abdominal pain with concurrent uncontrolled hypertension. Early diagnosis and intervention are crucial to reducing the mortality rate.
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- 2019
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19. The rare 13q33–q34 microdeletions: eight new patients and review of the literature
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Chana Vinkler, Lena Sagi-Dain, Amir Peleg, Shay Ben-Shachar, Lina Basel-Salmon, Rivka Sukenik-Halevy, Idit Maya, Yael Goldberg, Efrat Sofrin-Drucker, Ben Yehoshua Sagi Josefsberg, and Z. Appelman
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Microcephaly ,Adolescent ,Developmental Disabilities ,Genetic counseling ,Chromosome Disorders ,Context (language use) ,Biology ,Short stature ,Young Adult ,03 medical and health sciences ,Intellectual Disability ,Intellectual disability ,Genetics ,medicine ,Humans ,Copy-number variation ,Child ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,Chromosomes, Human, Pair 13 ,030305 genetics & heredity ,Infant, Newborn ,Infant ,medicine.disease ,Human genetics ,Hypotonia ,Chromosome Banding ,Phenotype ,Child, Preschool ,Female ,Chromosome Deletion ,medicine.symptom - Abstract
The objective of this study is to shed light on the phenotype and inheritance pattern of rare 13q33-q34 microdeletions. Appropriate cases were retrieved using local databases of two largest Israeli centers performing CMA analysis. In addition, literature search in PubMed, DECIPHER and ClinVar databases was performed. Local database search yielded eight new patients with 13q33.1-q34 microdeletions (three of which had additional copy number variants). Combined with 15 cases detected by literature search, an additional 23 cases were reported in DECIPHER database, and 17 cases from ClinVar, so overall 60 patients with isolated 13q33.1-q34 microdeletions were described. Developmental delay and/or intellectual disability were noted in the vast majority of affected individuals (81.7% = 49/60). Of the 23 deletions involving the 13q34 cytoband only, in 3 cases, developmental delay and/or intellectual disability was not reported. Interestingly, in two of these cases (66.7%), the deletions did not involve the terminal CHAMP1 gene, as opposed to 3/20 (15%) of patients with 13q34 deletions and neurocognitive disability. Facial dysmorphism and microcephaly were reported in about half of the overall cases, convulsions were noted in one-fifth of the patients, while heart anomalies, short stature and hypotonia each involved about 10-30% of the cases. None of the 13q33-q34 deletions were inherited from a reported healthy parent. 13q33-q34 microdeletions are rare chromosomal aberrations, associated with high risk for neurodevelopmental disability. The rarity of this chromosomal aberration necessitates continuous reporting and collection of available evidence, to improve the ability to provide accurate genetic counseling, especially in the context of prenatal setting.
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- 2019
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20. Prenatal and postnatal chromosomal microarray analysis in 885 cases of various congenital heart defects
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Liat Salzer-Sheelo, Uri Polak, Ayelet Barg, Sarit Kahana, Shiri Yacobson, Ifaat Agmon-Fishman, Cochava Klein, Reut Matar, Noa Rurman-Shahar, Lena Sagi-Dain, Lina Basel-Salmon, Idit Maya, and Rivka Sukenik-Halevy
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Chromosome Aberrations ,Heart Defects, Congenital ,Pregnancy ,Spiperone ,Prenatal Diagnosis ,Obstetrics and Gynecology ,Humans ,Female ,General Medicine ,Microarray Analysis ,Chromosomes ,Ultrasonography, Prenatal ,Retrospective Studies - Abstract
This study aimed to evaluate the prevalence of clinically significant (pathogenic and likely pathogenic) variants detected by chromosomal microarray (CMA) tests performed for prenatally and postnatally detected congenital heart defects.A retrospective evaluation of CMA analyses over a period of four years in a single tertiary medical center was performed. Detection rate of clinically significant variants was calculated in the whole cohort, prenatal vs. postnatal cases, and isolated vs. non-isolated CHD. This rate was compared to previously published control cohorts, and to a theoretical detection rate of noninvasive prenatal testing (NIPS; 5 chromosomes).Of the 885 cases of CHD, 111 (12.5%) clinically significant variants were detected, with no significant difference between the 498 prenatal and the 387 postnatal cases (10.8% vs. 14.7%, p = 0.08). In both groups, the detection rate was significantly higher for non-isolated vs. isolated CHD (76/339 = 22.4% vs. 35/546 = 6.4%, respectively, p 0.05). The detection rate was higher than the background risk in both groups, including cases of postnatal isolated CHD. 44% of abnormal findings in the prenatal setting would be detectable by NIPS.CMA should be performed for both prenatally and postnatally detected CHD, including postnatal cases of isolated CHD, while NIPS can be considered in specific scenarios.
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- 2021
21. Chromosomal Microarray Analysis in Pregnancies With Corpus Callosum or Posterior Fossa Anomalies
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Rivka Sukenik-Halevy, Lior Greenbaum, Idit Maya, Shlomit Rienstein, Adel Shalata, Lena Sagi-Dain, Amihood Singer, Michal Berkenstadt, Eldad Katorza, and Hagith Yonath
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Fetus ,medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,Microarray analysis techniques ,business.industry ,Obstetrics ,Posterior fossa ,Corpus callosum ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cohort ,Medicine ,Christian ministry ,Neurology (clinical) ,Background risk ,Detection rate ,business ,030217 neurology & neurosurgery ,Genetics (clinical) - Abstract
ObjectiveWe investigated the detection rate of clinically significant chromosomal microarray analysis (CMA) results in pregnancies with sonographic diagnosis of fetal corpus callosum anomalies (CCA) or posterior fossa anomalies (PFA).MethodsAll CMA tests in pregnancies with CCA or PFA performed between January 2015 and June 2020 were retrospectively evaluated from the Israeli Ministry of Health database. The rate of CMA with clinically significant (pathogenic or likely pathogenic) findings was calculated and compared to a local Israeli cohort of 5,541 pregnancies with normal ultrasound.ResultsOne hundred eighty-two pregnancies were enrolled: 102 cases with CCA and 89 with PFA (9 cases had both). Clinically significant CMA results were found in 7/102 of CCA (6.9%) and in 7/89 of PFA (7.9%) cases. The CMA detection rate in pregnancies with isolated CCA (2/57, 3.5%) or PFA (2/50, 4.0%) was lower than in nonisolated cases, including additional CNS and/or extra-CNS sonographic anomalies (CCA-5/45, 11.1%; PFA-5/39, 12.8%), but this was not statistically significant. However, the rate among pregnancies that had extra-CNS anomalies, with or without additional CNS involvement (CCA-5/24, 20.8%; PFA-5/29, 17.2%), was significantly higher compared to all other cases (p = 0.0075 for CCA; p = 0.035 for PFA). Risk of CMA with clinically significant results for all and nonisolated CCA or PFA pregnancies was higher compared to the background risk reported in the control cohort (p < 0.001), but was not significant for isolated cases.ConclusionsOur findings suggest that CMA testing is beneficial for the genetic workup of pregnancies with CCA or PFA, and is probably most informative when additional extra-CNS anomalies are observed.
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- 2021
22. Ten points to consider when providing genetic counseling for variants of incomplete penetrance and variable expressivity detected in a prenatal setting
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Rivka Sukenik-Halevy, Lena Sagi-Dain, Idit Maya, and Lina Basel-Salmon
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Pregnancy ,Pediatrics ,medicine.medical_specialty ,business.industry ,Genetic counseling ,MEDLINE ,Genetic Diseases, Inborn ,Obstetrics and Gynecology ,Prenatal diagnosis ,Genetic Counseling ,Penetrance ,Prenatal Care ,General Medicine ,medicine.disease ,Prenatal Diagnosis ,medicine ,Humans ,Female ,business - Published
- 2020
23. Should We Report 15q11.2 BP1-BP2 Deletions and Duplications in the Prenatal Setting?
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Tamar Tenne, Reut Matar, Ifaat Agmon-Fishman, Rivka Sukenik-Halevy, Shiri Yacobson, Lina Basel-Salmon, Sarit Kahana, Mordechai Shohat, Sharon Perlman, and Idit Maya
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0301 basic medicine ,medicine.medical_specialty ,Microarray ,phenotype ,lcsh:Medicine ,030105 genetics & heredity ,Article ,03 medical and health sciences ,chromosomal microarray ,Internal medicine ,medicine ,Clinical significance ,Copy-number variation ,penetrance ,Opting out ,business.industry ,Breakpoint ,lcsh:R ,BP1-BP2 ,deletions ,General Medicine ,15q11.2 ,Pathogenicity ,Penetrance ,030104 developmental biology ,Parental anxiety ,duplications ,business - Abstract
Copy number variations of the 15q11.2 region at breakpoints 1-2 (BP1-BP2) have been associated with variable phenotypes and low penetrance. Detection of such variations in the prenatal setting can result in significant parental anxiety. The clinical significance of pre- and postnatally detected 15q11.2 BP1-BP2 deletions and duplications was assessed. Of 11,004 chromosomal microarray tests performed in a single referral lab (7596 prenatal, 3408 postnatal), deletions were detected in 66 cases: 39 in prenatal tests (0.51%) and 27 in postnatal tests (0.79%). Duplications were detected in 94 cases: 62 prenatal tests (0.82%) and 32 postnatal tests (0.94%). The prevalence of deletions and duplications among clinically indicated prenatal tests (0.57% and 0.9%, respectively) did not differ significantly in comparison to unindicated tests (0.49% and 0.78%, respectively). The prevalence of deletions and duplications among postnatal tests performed for clinical indications was similar to the prevalence in healthy individuals (0.73% and 1% vs. 0.98% and 0.74%, respectively). The calculated penetrance of deletions and duplications over the background risk was 2.18% and 1.16%, respectively. We conclude that the pathogenicity of 15q11.2 BP1-BP2 deletions and duplications is low. Opting out the report of these copy number variations to both clinicians and couples should be considered.
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- 2020
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24. When phenotype does not match genotype: importance of 'real-time' refining of phenotypic information for exome data interpretation
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Lina, Basel-Salmon, Noa, Ruhrman-Shahar, Naama, Orenstein, Yael, Goldberg, Claudia, Gonzaga-Jauregui, Alan R, Shuldiner, Rivka, Sukenik-Halevy, Idit, Maya, Nurit, Magal, Ofir, Hagari, Noy, Azulay, Gabriel Arie, Lidzbarsky, and Lily, Bazak
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Phenotype ,Genotype ,Exome Sequencing ,Humans ,Exome ,Child ,Pedigree - Abstract
Clinical data provided to genetic testing laboratories are frequently scarce. Our purpose was to evaluate clinical scenarios where phenotypic refinement in proband's family members might impact exome data interpretation.Of 614 exomes, 209 were diagnostic and included in this study. Phenotypic information was gathered by the variant interpretation team from genetic counseling letters and images. If a discrepancy between reported clinical findings and presumably disease-causing variant segregation was observed, referring clinicians were contacted for phenotypic clarification.In 16/209 (7.7%) cases, phenotypic refinement was important due to (1) lack of cosegregation of disease-causing variant with the reported phenotype; (2) identification of different disorders with overlapping symptoms in the same family; (3) similar features in proband and family members, but molecular cause identified in proband only; and (4) previously unrecognized maternal condition causative of child's phenotype. As a result of phenotypic clarification, in 12/16 (75%) cases definition of affected versus unaffected status in one of the family members has changed, and in one case variant classification has changed.Detailed description of phenotypes in family members including differences in clinical presentations, even if subtle, are important in exome interpretation and should be communicated to the variant interpretation team.
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- 2020
25. The Yield of Chromosomal Microarray in Pregnancies Complicated with Fetal Growth Restriction Can Be Predicted According to Clinical Parameters
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Lena Sagi-Dain, Rachel Michaelson-Cohen, Rivka Sukenik Halevy, Amihood Singer, Hagit Daum, Keren Tzadikevitch Geffen, Shay Ben-Shachar, Michal Feingold-Zadok, Lior Greenbaum, and Idit Maya
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Embryology ,medicine.medical_specialty ,Microarray ,Intrauterine growth restriction ,Cohort Studies ,Pregnancy ,Fetal growth ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Chromosome Aberrations ,Fetal Growth Retardation ,business.industry ,Microarray analysis techniques ,Obstetrics ,Obstetrics and Gynecology ,Gestational age ,General Medicine ,Odds ratio ,medicine.disease ,Microarray Analysis ,Pediatrics, Perinatology and Child Health ,Cohort ,Female ,business - Abstract
Introduction: We evaluated the yield of chromosomal microarray analysis in pregnancies complicated with fetal growth restriction (FGR) according to specific clinical parameters. Methods: The study was based on national records from the Israeli Ministry of Health. Chromosomal microarray analyses of amniocenteses performed nationwide for the indication of FGR, from January 2016 to March 2018, were included. The CMA yield was compared to 2 cohorts that reported the background risk. Results: Of 174 tests performed for the indication of FGR, there were 11 cases with a pathogenic/likely pathogenic result (6.3%). The yield of CMA was significantly higher in cases with major structural findings (29.4 vs. 3.4%, p = 0.001), compared to isolated FGR but not for minor structural findings (6.1 vs. 3.4%, p = 0.5). The rate of chromosomal aberrations was significantly higher for all cases with FGR, when compared to the background risk of a cohort of normal pregnancies (odds ratio [OR] 4.7, 95% CI 2.5–9 and OR 6.09, 95% CI 3.2–11.4) but not for isolated cases or cases diagnosed after 24 weeks of pregnancy. Conclusions: Chromosomal microarray analysis should be performed for all pregnancies complicated with FGR diagnosed before 24 weeks and for cases with major structural anomalies.
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- 2020
26. Chromosomal microarray should be performed for cases of fetal short long bones detected prenatally
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Keren, Tzadikevitch Geffen, Amihood, Singer, Idit, Maya, Lena, Sagi-Dain, Morad, Khayat, Shay, Ben-Shachar, Hagit, Daum, Rachel, Michaelson-Cohen, Michal, Feingold-Zadok, and Rivka, Sukenik Halevy
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Chromosome Aberrations ,Fetal Growth Retardation ,DNA Copy Number Variations ,Pregnancy Outcome ,Chromosome Disorders ,Humerus ,Microarray Analysis ,Ultrasonography, Prenatal ,Cohort Studies ,Fetus ,Pregnancy ,Prenatal Diagnosis ,Prevalence ,Humans ,Female ,Femur - Abstract
To investigate the prevalence of pathogenic and likely-pathogenic variants detected by chromosomal microarray analysis (CMA), among pregnancies with fetal short long bones diagnosed by ultrasound.The study cohort was based on cases of chromosomal microarray analyses performed nationwide for the indication of short long bones.CMA was performed in 66 cases of short long bones. There were 4 cases with a pathogenic/likely pathogenic result (6%). The rate of chromosomal abnormalities was significantly higher compared to the background risk for copy number variations (CNVs) in pregnancies with no sonographic anomalies (P 0.001). The yield of CMA in our cohort was significantly higher for both isolated and non-isolated cases, for cases in which the lowest estimated bone length percentile was above the 3rd percentile (below 5th percentile), and for cases diagnosed with short long bones after 22 weeks but not for cases diagnosed after 24 weeks.The yield of CMA in cases with short long bones (both isolated and non-isolated) is significantly higher than the background risk for chromosomal anomalies in pregnancies with no sonographic anomalies. This suggests that CMA should be offered in pregnancies with a diagnosis of fetal short long bones.
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- 2020
27. Teaching clinicians practical genomic medicine: 7 years' experience in a tertiary care center
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Rachel, Michaelson-Cohen, Liat, Salzer-Sheelo, Rivka, Sukenik-Halevy, Arie, Koifman, Avi, Fellner, Adi, Reches, Daphna, Marom, Doron M, Behar, Efrat, Sofrin-Drucker, Gal, Zaks-Hoffer, Monika, Weiss-Hubshmann, Naama, Oresntein, Nesia, Kropach-Gilad, Noa, Rhurman-Shahar, Noa Shefer, Averbuch, Nurit, Magal, Lily, Bazak, Sagi, Josefberg, Reut, Matar, Yael, Goldberg, Mordechai, Shohat, Lina, Basel-Salmon, and Idit, Maya
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Tertiary Care Centers ,Surveys and Questionnaires ,Internship and Residency ,Medicine ,Genomics - Abstract
Increased implementation of complex genetic technologies in clinical practice emphasizes the urgency of genomic literacy and proficiency for medical professionals. We evaluated our genomic education model.We assessed the 5-day, extended format program, encompassing lectures, videos, interactive tests, practice cases, and clinical exercises. Pre- and post questionnaires assessed knowledge change, using t-tests to compare groups. Satisfaction on program completion and after 3 years were evaluated. Implementation in other centers determined acceptability.During 2012-2018, 774 clinicians from multiple disciplines and career stages attended 35 programs; 334 (43%) attended the 5-day extended format. Evaluations showed significant improvement of genomic literacy (mean 15.05/100 points, p 0.001). Residents initially had higher scores than specialists (pre: 66.3 ± 17.3 vs. 58.7 ± 16.6, respectively, p = 0.002); both significantly improved, with specialists "catching up" (post: 79.1 ± 17.2 vs. 75.7 ± 15.9, nonsignificant (NS)); there was a similar trend between fellows and subspecialists (pre: 70 ± 18 vs. 59.4 ± 16.4, respectively, p = 0.007; post: 78.6 ± 16.4 vs. 73.2 ± 17.7, respectively, NS). Younger specialists (≤10 years residency) had significantly higher pre- and post scores. Absolute improvement in scores did not depend on medical specialties.Our program is effective in improving genomics literacy for clinicians, irrespective of career length or expertise, and could be a model for improving skills in practical genomics for all medical professionals.
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- 2020
28. Prediction of the efficacy of dinoprostone slow release vaginal insert (Propess) for cervical ripening: A prospective cohort study
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Yair Daykan, Daniella Navve, Tal Biron-Shental, Mor Bustan, Netanella Miller, and Rivka Sukenik-Halevy
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medicine.medical_specialty ,Pregnancy ,030219 obstetrics & reproductive medicine ,Obstetrics ,business.industry ,Vaginal delivery ,medicine.medical_treatment ,food and beverages ,Obstetrics and Gynecology ,Gestational age ,Intrauterine growth restriction ,Ripening ,medicine.disease ,Dinoprostone ,03 medical and health sciences ,0302 clinical medicine ,Labor induction ,medicine ,030212 general & internal medicine ,business ,Prospective cohort study - Abstract
Aim To evaluate factors predictive of the success of dinoprostone slow release vaginal insert for cervical ripening. Methods A total of 169 women who underwent cervical ripening with dinoprostone slow release vaginal insert were included in the study cohort. The correlation between parameters present before cervical ripening with dinoprostone slow release and its success, as well as complications and adverse outcomes were analyzed. Results Dinoprostone slow release vaginal insert was successful in achieving vaginal delivery in 148 of 169 (87.6%), while sufficient ripening was achieved in 140 (83%) cases. Factors associated with successful vaginal delivery were multiparity and younger gestational age at delivery. Factors predictive of the success of cervical ripening with dinoprostone slow release vaginal insert were lower body mass index (BMI), higher parity and perceived contractions prior to insertion. Intrauterine growth restriction was associated with a significant risk for dinoprostone insert removal. Neonatal outcomes were similar in cases of successful or failed ripening. Conclusion The success of cervical ripening with dinoprostone slow release vaginal insert can be predicted by factors that can be recognized at admission.
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- 2018
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29. What are the prevalence, characteristics and significance of fetal lateral neck cysts detected in an early anatomical scan?
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Tal Biron-Shental, Ofer Markovitch, Rivka Sukenik Halevy, Anat Hershko-Klement, Jordana Mashiach Friedler, and Ronnie Tepper
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Adult ,medicine.medical_specialty ,Heart malformation ,Aneuploidy ,Ultrasonography, Prenatal ,Cohort Studies ,03 medical and health sciences ,Fetus ,0302 clinical medicine ,Pregnancy ,Prevalence ,medicine ,Humans ,Cyst ,030212 general & internal medicine ,FLNC ,Child ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,Cysts ,Obstetrics ,business.industry ,Pregnancy Outcome ,Obstetrics and Gynecology ,Prenatal Care ,General Medicine ,medicine.disease ,Work-up ,Fetal Diseases ,Pregnancy Trimester, First ,Cohort ,Amniocentesis ,Female ,Nuchal Translucency Measurement ,business ,Neck - Abstract
This study evaluated the association of fetal lateral neck cysts (FLNC) with adverse pregnancy outcomes, in relation to specific sonographic characteristics and co-existing findings. Pregnancies in which FLNC were detected by a single examiner in early anatomical scans (14–16 weeks) were included. Data regarding the pregnancy and its outcome were retrieved from telephone-based questionnaires, patient charts and from the examiner’s reports. 654 cases of FLNC were detected among 9446 early anatomical scans (6.9%). Complete data regarding 219 pregnancies were available. FLNC were significantly more prevalent in males (65.2%). The prevalence of heart malformations was 3.2% [all were non-isolated cases or with abnormal nuchal translucency (NT) and/or nuchal fold (NF)]. Amniocentesis performed in 165 pregnancies was abnormal in 1.2%. Among 206 children born from this cohort, adverse medical outcomes were reported in 5.3%. The likelihood of adverse pregnancy outcomes was significantly higher in non-isolated cases and in cases with abnormal NT or NF. Sonographic characteristics such as cyst size and bilateral findings were not linked to adverse pregnancy outcomes. Isolated FLNC are benign findings which do not require additional work up. FLNC with additional sonographic abnormalities are associated with a significantly increased risk for adverse pregnancy outcomes.
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- 2018
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30. Challenges in variant interpretation in prenatal exome sequencing
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Lina, Basel-Salmon and Rivka, Sukenik-Halevy
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Phenotype ,Pregnancy ,Prenatal Diagnosis ,Mutation ,Exome Sequencing ,Genetics ,Humans ,Female ,General Medicine ,Genetics (clinical) - Abstract
The use of exome sequencing (ES) in the prenatal setting improves the diagnostic yield of genetic testing for fetuses with ultrasound anomalies. However, while the purpose of ES is to explain the fetal phenotype, secondary or incidental findings unrelated to the observed abnormalities might be detected. Recently, requests for ES in fetuses with no sonographic abnormalities have been increasing, raising serious ethical and medico-legal concerns. Variant interpretation is complex even in the postnatal setting and performing broad genomic data analyses in the prenatal setting presents additional dilemmas. This article discusses challenges and questions related to prenatal ES, including variant interpretation of incidental findings in cases of indicated prenatal ES, as well as in situations where ES is performed in asymptomatic fetuses.
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- 2022
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31. The impact of third-trimester genetic counseling
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Reuven Sharony, Tal Biron-Shental, Rivka Sukenik-Halevy, Mark I. Evans, Offra Engel, and Shira Litz-Philipsborn
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Adult ,medicine.medical_specialty ,Referral ,Pregnancy Trimester, Third ,Genetic counseling ,Decision Making ,Genetic Counseling ,Autopsy ,Ultrasonography, Prenatal ,03 medical and health sciences ,Fetus ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,030225 pediatrics ,medicine ,Humans ,Retrospective Studies ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Obstetrics ,Infant, Newborn ,Obstetrics and Gynecology ,Abortion, Induced ,Retrospective cohort study ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Echocardiography ,Amniocentesis ,Patient Compliance ,Female ,business ,Fetal echocardiography - Abstract
To evaluate the impact of genetic counseling (GC) during the third trimester by analyzing changes in pregnancy management and the correlation with postnatal findings. This was a retrospective study. Pregnancy course and neonatal follow-up were analyzed according to the reason for referral and implementation of recommendations. The records of neonates born to 181 women were retrieved. Fifty-two women (group 1—29%) qualified for pregnancy termination under Israeli guidelines and laws, and 129 (group 2—71%) were not at the time they were referred. By another division: 104 women (group 3—57%) followed the physician’s diagnostic recommendations completely after counseling including amniocentesis, fetal MRI, targeted ultrasound scans, fetal echocardiography. Seventy-seven declined amniocentesis (group 4—43%). Additional abnormalities were detected postpartum in all groups without statistically difference: 3/52 (10%) in group 1, 9/129 (7%) in group 2, 6/104 (6%) in group 3, and 6/77 (8%) in group 4). GC in the third trimester of pregnancy provided the couple with a sharper more focused picture and assisted them to perceive the significance of new, significant fetal findings which attest to the value of the GC.
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- 2018
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32. Diagnostic accuracy, work-up, and outcomes of pregnancies with clubfoot detected by prenatal sonography
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Ofer Markovitch, Tal Biron-Shental, Maya Sharon-Weiner, Ami Fishman, Ronnie Tepper, and Rivka Sukenik-Halevy
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musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Clubfoot ,Chorionic villus sampling ,03 medical and health sciences ,0302 clinical medicine ,medicine ,reproductive and urinary physiology ,Genetics (clinical) ,Gynecology ,030222 orthopedics ,Pregnancy ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Obstetrics ,Ultrasound ,Obstetrics and Gynecology ,Retrospective cohort study ,medicine.disease ,humanities ,Work-up ,Cohort ,Amniocentesis ,business - Abstract
Objective To assess diagnostic accuracy, related findings, and outcomes of fetuses with clubfoot. Methods Sonographic characteristics, pregnancy work-up, and postnatal outcomes were evaluated in 109 fetuses with clubfoot. Results Among 40 320 prenatal ultrasound anomaly scans, clubfoot was diagnosed in 150 (0.37%). Analysis included 108 pregnancies (72%) with 109 fetuses. Bilateral clubfoot was diagnosed in 51/109 (46.7%) fetuses and unilateral in 58/109 (53.2%). Clubfoot was diagnosed as an isolated anomaly in 76/109 (69.7%) and complex in 33/109 (30.2%). Amniocentesis or chorionic villus sampling in 48/109 (44%) yielded 6 (12.5%) with abnormalities (5.5% of the entire cohort). Diagnosis was confirmed in 65/91 (71.4%) liveborn infants. In singletons, 7/63 (11.1%) cases considered isolated on ultrasound had additional anomalies postpartum and 8/14 (57.1%) complex cases were verified after birth. Sonographic diagnosis of clubfoot was verified postpartum in more singletons than twins (p = 0.05). Bilateral clubfoot was verified postpartum more often than unilateral [29/33 (87.9%) vs. 29/44 (65.9%), respectively; p = 0.03]. Bilateral clubfoot resulted in additional prenatal testing without increased likelihood of finding additional anomalies and was associated with more surgical interventions postnatally. Conclusions Prenatal ultrasound diagnosis of clubfoot is more accurate in singletons with bilateral findings. Bilateral findings do not increase the likelihood of additional anomalies. Karyotyping should be considered even with isolated clubfoot. © 2017 John Wiley & Sons, Ltd.
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- 2017
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33. The yield of chromosomal microarray analysis among pregnancies terminated due to fetal malformations
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Eyal Reinstein, Tamar Tenne, Tal Biron-Shental, Netanella Miller, Idit Maya, Yael Pasternak, Gil Shechter-Maor, Rivka Sukenik Halevy, and Yair Daykan
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0301 basic medicine ,DNA Copy Number Variations ,030105 genetics & heredity ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Fetus ,Pregnancy ,Prenatal Diagnosis ,Medicine ,Humans ,Copy-number variation ,health care economics and organizations ,Chromosome Aberrations ,030219 obstetrics & reproductive medicine ,Microarray analysis techniques ,business.industry ,Obstetrics and Gynecology ,medicine.disease ,Microarray Analysis ,humanities ,Yield (chemistry) ,Karyotyping ,Pediatrics, Perinatology and Child Health ,Female ,Detection rate ,business - Abstract
Chromosomal microarray analysis (CMA) is preferred for genetic work-up when fetal malformations are detected prenatally.To assess the detection rate of CMA after pregnancy termination due to abnormal ultrasound findings.CMA was successfully performed in 71 pregnancies using fetal DNA (mainly from skin) or placenta. Data regarding clinical background, pregnancy work-up, and CMA were analyzed.Findings were abnormal in 17 cases (23.9%), of which 13 were detectable by karyotype. The incremental yield of CMA was 4/71 (5.6%); 1/32 (3.1%) for cases with an isolated anomaly and 3/39 (7.7%) for cases with nonisolated anomalies.CMA yield from terminated pregnancies was 23.9%. Although most chromosomal abnormalities are detectable by karyotype, CMA does not require viable dividing cells; hence, it is more practical for work-up after termination. In most cases, the diagnosis was followed by consultation regarding the risk of recurrence and recommendations for testing in subsequent pregnancies.
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- 2020
34. Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures
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Henry Houlden, Mary A. O’Connell, Tiong Yang Tan, Ingo Helbig, Jane Juusola, Mayada Helal, Jiří Sedmík, Lynn Pais, Lior Cohen, Lina Basel-Salmon, Katherine B. Howell, Mark Fitzgerald, Rivka Sukenik Halevy, Susan M. White, Rachel Straussberg, Simon Sadedin, Liam Keegan, Reza Maroofian, Wendy K. Chung, and John Christodoulou
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Male ,0301 basic medicine ,Microcephaly ,Adenosine Deaminase ,RNA Splicing ,RNA-binding protein ,Biology ,Article ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Seizures ,Intellectual Disability ,Intellectual disability ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Child ,Gene ,Alleles ,Genetics (clinical) ,Alternative splicing ,Genetic Variation ,RNA-Binding Proteins ,medicine.disease ,Alternative Splicing ,HEK293 Cells ,030104 developmental biology ,RNA editing ,Child, Preschool ,RNA splicing ,030217 neurology & neurosurgery - Abstract
The RNA editing enzyme ADAR2 is essential for the recoding of brain transcripts. Impaired ADAR2 editing leads to early-onset epilepsy and premature death in a mouse model. Here, we report bi-allelic variants in ADARB1, the gene encoding ADAR2, in four unrelated individuals with microcephaly, intellectual disability, and epilepsy. In one individual, a homozygous variant in one of the double-stranded RNA-binding domains (dsRBDs) was identified. In the others, variants were situated in or around the deaminase domain. To evaluate the effects of these variants on ADAR2 enzymatic activity, we performed in vitro assays with recombinant proteins in HEK293T cells and ex vivo assays with fibroblasts derived from one of the individuals. We demonstrate that these ADAR2 variants lead to reduced editing activity on a known ADAR2 substrate. We also demonstrate that one variant leads to changes in splicing of ADARB1 transcript isoforms. These findings reinforce the importance of RNA editing in brain development and introduce ADARB1 as a genetic etiology in individuals with intellectual disability, microcephaly, and epilepsy.
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- 2020
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35. Does parity affect pregnancy outcomes in the elderly gravida?
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Gil, Shechter-Maor, Dana, Sadeh-Mestechkin, Yael, Ganor Paz, Rivka, Sukenik Halevy, Ofer, Markovitch, and Tal, Biron-Shental
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Adult ,Cohort Studies ,Pregnancy Complications ,Parity ,Pregnancy ,Pregnancy Outcome ,Humans ,Female ,Gravidity ,Maternal Age ,Retrospective Studies - Abstract
To identify whether older primiparas have more complications than do women who continue to deliver children into their late reproductive age. Patients of at least 35 years of age at delivery were included. Within this cohort, data from primiparous and multiparous women were compared.This retrospective study was based on electronic medical records from a single academic center, with more than 7000 deliveries annually. The impact of parity on maternal complications was assessed using a multivariate logistic regression model that adjusted for baseline maternal characteristics and medical history.During the study period, there were 54 283 deliveries in our medical center. A total of 13,982 (25.7%) patients were at least 35 years old at delivery. The rate of twin pregnancy was higher in the primiparous group (1.9%) as compared to the multiparous group (0.8%, 95% CI 0.30-0.64, P 0.001), as was the incidence of delivery prior to 34 weeks (6.1% of the primiparas versus 2.9% of the multiparas, P 0.001, OR 2.16, 95% CI 1.75-2.68); hypertensive disorders (3.9% versus 1.7%, P 0.001, 95% CI 0.33-0.57); diabetes (4.6% versus 3.2%, P = 0.003, 95% CI 0.55-0.88); and IUGR (10.5% versus 4.7%, P 0.001, 95% CI 0.35-049), respectively. The increased risk for pre-term delivery, hypertensive disorders, diabetes, and IUGR was maintained after logistic regression analysis.We found that pregnancy complications typical to older parous women are significantly more common among primiparas, indicating that not only older age, but also having a first child relatively late in the reproductive period contributes to adverse pregnancy outcomes.
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- 2019
36. Microarray findings in pregnancies with oligohydramnios - a retrospective cohort study and literature review
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Dorit Lev, Tamar Tenne, Shay Ben Shachar, Amihood Singer, Lena Sagi-Dain, Idit Maya, and Rivka Sukenik-Halevy
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0301 basic medicine ,Adult ,medicine.medical_specialty ,Microarray ,DNA Copy Number Variations ,Oligohydramnios ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pregnancy ,Medicine ,Humans ,Likely pathogenic ,Retrospective Studies ,Chromosome Aberrations ,business.industry ,Obstetrics ,Obstetrics and Gynecology ,Retrospective cohort study ,medicine.disease ,Microarray Analysis ,Confidence interval ,030104 developmental biology ,Relative risk ,Pediatrics, Perinatology and Child Health ,Cohort ,Christian ministry ,Female ,business ,030217 neurology & neurosurgery - Abstract
Objective To explore the risk for abnormal chromosomal microarray analysis (CMA) findings in pregnancies with oligohydramnios. Methods Data from all CMA analyses performed due to oligohydramnios between 2013 and 2017 were retrospectively obtained from the Israeli Ministry of Health database. The rate of clinically significant (pathogenic and likely pathogenic) findings was compared to a local cohort of pregnancies with normal ultrasound, yielding a 1.4% rate of abnormal CMA results. In addition, a search was conducted through the PubMed database addressing the issue. Results Fifty CMA analyses were performed due to oligohydramnios. The 2% risk for clinically significant CMA finding in pregnancies with oligohydramnios did not differ from the control population of 5541 pregnancies with normal ultrasound – relative risk (RR) 1.4 [95% confidence interval (CI) 0.2–10.2]. Literature search yielded 394 titles, of which four relevant articles were selected, all using fetal karyotyping. Conclusion There is yet insufficient evidence to support invasive prenatal testing in pregnancies with isolated oligohydramnios.
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- 2019
37. Clinical aspects of prenatally detected congenital heart malformations and the yield of chromosomal microarray analysis
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Tal Biron-Shental, Rivka Sukenik-Halevy, Alex Levi, Reli Hershkovitz, Arie Koifman, Yoav Alpert, and Shay Sukenik
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Pregnancy ,medicine.medical_specialty ,Pathology ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,Heart malformation ,Obstetrics ,Microarray analysis techniques ,business.industry ,Obstetrics and Gynecology ,Gestational age ,030204 cardiovascular system & hematology ,medicine.disease ,humanities ,03 medical and health sciences ,0302 clinical medicine ,Nuchal Translucency Measurement ,medicine ,Family history ,business ,Fetal echocardiography ,health care economics and organizations ,Genetics (clinical) ,Genetic testing - Abstract
Objective The yield of chromosomal microarray analysis (CMA) for prenatally detected congenital heart defects (CHD) is 6.6-19.2%. We evaluated the yield of CMA in cases of prenatally detected CHD in regard to specific clinical characteristics. Methods Data from 192 cases of CHD including type, clinical and familial background, work-up performed during the pregnancy, and pregnancy outcomes were collected. Results Fetal echocardiography was performed in all cases. 61.4% of CHD were suspected by ultrasound. There was a positive family history (FH) in 15.7%. Abnormal nuchal translucency or umbilical cord anomalies were detected in 1.7% and 5.9% respectively and 45.1% were isolated cases. In 11 of 96 cases in which genetic testing was performed, either karyotype and/or CMA were abnormal (11.5%). The detection rate of CMA (performed in 72 cases) was 9.7%. The yield of CMA was similar in simple cases, isolated cases and cases with a positive FH. CMA was abnormal in 7.3% of ventricular septal defect (VSD) cases. Conclusion Most cases of prenatally detected CHD had no additional extra-cardiac, sonographic findings suggesting increased risk for CHD. The yield of CMA testing was significant in all clinical scenarios including simple heart malformations, isolated cases and cases with a positive FH.
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- 2016
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38. The time-consuming demands of the practice of medical genetics in the era of advanced genomic testing
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Mark Ludman, Annick Raas-Rothschild, Rivka Sukenik-Halevy, and Shay Ben-Shachar
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0301 basic medicine ,medicine.medical_specialty ,Time Factors ,Cost effectiveness ,Genetics, Medical ,Health Personnel ,media_common.quotation_subject ,Workload ,030105 genetics & heredity ,Time-Consuming ,Medical care ,Patient care ,03 medical and health sciences ,Surveys and Questionnaires ,medicine ,Humans ,Pharmacology (medical) ,Quality (business) ,Genetic Testing ,Referral and Consultation ,Biological Psychiatry ,Genetics (clinical) ,media_common ,Pharmacology ,Internet ,Pregnancy ,business.industry ,Genomics ,medicine.disease ,Psychiatry and Mental health ,Pediatric patient ,Neurology ,Family medicine ,Cohort ,Medical genetics ,Neurology (clinical) ,Personalized medicine ,business - Abstract
Clinical genetics services are time- and labor-intensive. With increasing pressure for cost-effective medical care, the means of providing medical genetics services need to be evaluated in the current era of new genomic technologies. An anonymous online survey regarding activities linked to medical genetics practice was administered to an international cohort of professionals. Among 151 responses, the reported average time required for pediatric, oncogenetic, pregnancy with a malformed fetus, and preamniocentesis counseling sessions was 48, 37, 40, and 18 min, respectively. The time required to prepare a summary letter followed a similar pattern. Professionals with less experience needed more time for specific activities. The time required for the total workup of a pediatric patient ranged from 1 h and 48 min to 4 h, most of which was associated with indirect activities. Professionals performing one type of consultation (74% pediatric geneticists) perform fewer consultations per week. Respondents’ narrative comments reflected the complexity of the work and challenges faced. Clinical genetics is a time-consuming profession with increased demands related to advanced genetic and genomic testing. Further consideration is required to determine how to adapt these changes to the demands of cost-effectiveness without compromising the quality of patient care. Genet Med 18 4, 372–377.
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- 2016
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39. Telomere Homeostasis and Senescence Markers Are Differently Expressed in Placentas From Pregnancies With Early- Versus Late-Onset Preeclampsia
- Author
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Tal Biron-Shental, Sivan Farladansky-Gershnabel, Debora Kidron, Aliza Amiel, Hilah Gal, Valery Krizhanovsky, and Rivka Sukenik-Halevy
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0301 basic medicine ,Senescence ,Adult ,medicine.medical_specialty ,Time Factors ,Placenta ,Reproductive medicine ,Physiology ,Gestational Age ,Preeclampsia ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Telomere Homeostasis ,Pre-Eclampsia ,Pregnancy ,Medicine ,Humans ,Cellular Senescence ,Fetus ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics and Gynecology ,medicine.disease ,Telomere ,Trophoblasts ,030104 developmental biology ,Embryology ,Gestation ,Female ,business ,Biomarkers - Abstract
Early-onset preeclampsia (EOPE;34 weeks' gestation) usually has more severe morbidity for the mother and fetus compared to late-onset preeclampsia (LOPE). Telomere homeostasis is disrupted in preeclampsia (PE) and senescence markers are increased. The pathophysiologic differences between early and LOPE are not fully unraveled yet.We studied placental biopsies from 7 pregnancies with EOPE, 6 pregnancies with LOPE, and 13 healthy gestational age-matched controls. Telomere length and aggregate formation were assessed using qualitative fluorescence in situ hybridization and electronic quantitative methods. Senescence markers were evaluated including senescence-associated heterochromatin foci, β-galactosidase (SAβ-Gal), and P16 staining, as was the expression of P16 complementary DNA (cDNA) using real-time quantitative polymerase chain reaction (RT-qPCR).There were no differences in maternal age, gravidity, parity, body mass index, and mode of conception between the study and the control groups. The percentage of trophoblasts with short telomeres was higher in placental samples from EOPE (52.61% [12.27%]) versus LOPE (28.72% [10.14%]); both were higher compared to controls (7.53% [5.14%],Impaired telomere homeostasis and senescence markers are more prominent in EOPE versus LOPE. These findings may contribute to our understanding of the pathophysiology and explain their different clinical presentations and outcomes.
- Published
- 2018
40. Mutations in the fourth β-propeller domain of LRP4 are associated with isolated syndactyly with fusion of the third and fourth fingers
- Author
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Bo Heinz, Huan-Chieh Chien, Martin Kircher, Michael J. Bamshad, Nadav Ahituv, Rivka Sukenik Halevy, and Deborah A. Nickerson
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0301 basic medicine ,limb malformations ,Protein domain ,LRP4 ,Clinical Sciences ,Limb Deformities, Congenital ,Mutation, Missense ,Biology ,Article ,03 medical and health sciences ,Congenital ,Rare Diseases ,Genetic etiology ,Exome Sequencing ,medicine ,Extracellular ,Genetics ,Humans ,Syndactyly ,University of Washington Center for Mendelian Genomics ,Genetics (clinical) ,Exome sequencing ,LDL-Receptor Related Proteins ,Genetics & Heredity ,Homozygote ,Human Genome ,Wnt signaling pathway ,LRP6 ,syndactyly ,medicine.disease ,Phenotype ,Wnt signaling ,Pedigree ,Limb Deformities ,030104 developmental biology ,Mutation ,Missense - Abstract
Isolated hand syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover two novel variants, chr11 g.46896373C>G; p.D1403H and chr11 g.46893078G>T; p.Q1564K, in LRP4 in a child with isolated bilateral syndactyly of the third and fourth fingers. Each variant was inherited from a different parent and neither parent was affected. Variants in LRP4 have been previously associated with syndactyly in Cenani-Lenz syndactyly syndrome and Sclerosteosis 2, but have not been reported in individuals with isolated syndactyly. LRP4 inhibits LRP6/LRP5-mediated activation of canonical Wnt signaling and mediates sclerostin-dependent inhibition of bone formation. p.D1403H and p.Q1564K are located within the fourth β-propeller of the extracellular protein domain that has yet to be associated with human disease. Functional analyses of p.D1403H and p.Q1564K show that they significantly decrease LRP4's inhibition of Wnt signaling. These results suggest that variants in the fourth β-propeller of the extracellular protein domain may cause a phenotype distinct from previously characterized LRP4 variants.
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- 2018
41. The association between maternal serum first trimester free βhCG, second trimester intact hCG levels and foetal growth restriction and preeclampsia
- Author
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Tal Biron-Shental, Eyal Reinstein, Debora Kidron, Rivka Sukenik-Halevy, Reuven Sharony, Mira Manor, Ron Maymon, and Maya Sharon-Weiner
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Gestational Age ,Chorionic Gonadotropin ,Preeclampsia ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Growth restriction ,Pre-Eclampsia ,Second trimester ,Pregnancy ,Foetal growth ,medicine ,Humans ,Chorionic Gonadotropin, beta Subunit, Human ,030212 general & internal medicine ,reproductive and urinary physiology ,Retrospective Studies ,030219 obstetrics & reproductive medicine ,Fetal Growth Retardation ,business.industry ,Free βhcg ,Obstetrics and Gynecology ,medicine.disease ,female genital diseases and pregnancy complications ,First trimester ,Pregnancy Trimester, First ,Pregnancy Trimester, Second ,embryonic structures ,Free beta hcg ,Female ,business - Abstract
The purpose of this study was to analyse the association between free beta hCG (fβhCG) increased levels and pregnancy complications (PC), foetal growth restriction (FGR) and preeclampsia (PE). This connection was evaluated in two stages (i) investigating the association between those PC with first trimester fβhCG and second trimester intact hCG (ihCG), and (ii) studying the association between these two analytes in the same pregnancy. This was a retrospective study in two settings: medical centre that provided data on fβhCG and ihCG levels in pregnancies with FGR and PE, and central laboratory that provided fβhCG and ihCG levels that were compared in the same pregnancy. No association was found between those PC and the hCG analytes, except for elevated ihCG levels and FGR. Elevated fβhCG (3.00 MoM) was found in 570/16,849 (3.4%) women. However, only 14% of whom had elevated second trimester ihCG. A positive correlation was found between the magnitude of first trimester fβhCG levels and the percentage of women who had elevated second trimester ihCG. This association was determined by the magnitude of the elevation of fβhCG levels. Impact statement What is already known on this subject: The two analytes, first trimester fβhCG and second trimester ihCG, are independently produced and parameters of the biochemical screening during pregnancy. What the results of this study add: Referring to 3.00 MoM as cut-off levels, most pregnancies with elevated levels of first trimester fβhCG will have normal ihCG second trimester levels. What the implications are of these findings for clinical practice and/or further research: The risk of developing pregnancy complications, FGR and PE should be associated with second trimester ihCG levels. About 3.5% of women had high fβhCG levels during the first trimester. However, only 14% also had increased ihCG levels, defined as 3.00 MoM; additional studies are needed to explore the association between increased first trimester fβhCG levels and the risk of developing pregnancy complications, independent of ihCG levels in the second trimester.
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- 2018
42. A point mutation in the pre-ZRS disrupts sonic hedgehog expression in the limb bud and results in triphalangeal thumb-polysyndactyly syndrome
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Martijn Baas, Steven E.R. Hovius, Rivka Sukenik-Halevy, Deon J Venter, Picard Nguyen, Annelies de Klein, Hannie Douben, Renee Gallagher, Robert-Jan H. Galjaard, Christianne A. van Nieuwenhoven, Jacob W P Potuijt, Sigrid M. A. Swagemakers, Peter J. van der Spek, Nadav Ahituv, Plastic and Reconstructive Surgery and Hand Surgery, Clinical Genetics, and Pathology
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Male ,0301 basic medicine ,Limb Buds ,Genetic Linkage ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Congenital Abnormalities ,Mice ,03 medical and health sciences ,Limb bud ,0302 clinical medicine ,Exome Sequencing ,medicine ,Animals ,Humans ,Point Mutation ,Limb development ,Genetic Predisposition to Disease ,Hedgehog Proteins ,Sonic hedgehog ,Enhancer ,In Situ Hybridization, Fluorescence ,Genetics (clinical) ,Mutation ,biology ,Point mutation ,Membrane Proteins ,Molecular biology ,Pedigree ,Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,Enhancer Elements, Genetic ,030104 developmental biology ,Gene Expression Regulation ,Zone of polarizing activity ,biology.protein ,Female ,Ectopic expression ,Chromosomes, Human, Pair 7 ,Mandibulofacial Dysostosis ,030217 neurology & neurosurgery - Abstract
Item does not contain fulltext PURPOSE: The zone of polarizing activity regulatory sequence (ZRS) is an enhancer that regulates sonic hedgehog during embryonic limb development. Recently, mutations in a noncoding evolutionary conserved sequence 500 bp upstream of the ZRS, termed the pre-ZRS (pZRS), have been associated with polydactyly in dogs and humans. Here, we report the first case of triphalangeal thumb-polysyndactyly syndrome (TPT-PS) to be associated with mutations in this region and show via mouse enhancer assays how this mutation leads to ectopic expression throughout the developing limb bud. METHODS: We used linkage analysis, whole-exome sequencing, Sanger sequencing, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, single-nucleotide polymorphism array, and a mouse transgenic enhancer assay. RESULTS: Ten members of a TPT-PS family were included in this study. The mutation was linked to chromosome 7q36 (LOD score 3.0). No aberrations in the ZRS could be identified. A point mutation in the pZRS (chr7:156585476G>C; GRCh37/hg19) was detected in all affected family members. Functional characterization using a mouse transgenic enhancer essay showed extended ectopic expression dispersed throughout the entire limb bud (E11.5). CONCLUSION: Our work describes the first mutation in the pZRS to be associated with TPT-PS and provides functional evidence that this mutation leads to ectopic expression of this enhancer within the developing limb.
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- 2018
43. Telomeres are shorter in placentas from pregnancies with uncontrolled diabetes
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Meytal Liberman, Tal Biron-Shental, R. Kats, Rivka Sukenik-Halevy, H. Naboani, and Aliza Amiel
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Adult ,Blood Glucose ,Senescence ,Placenta ,Biology ,Andrology ,Pregnancy ,Diabetes mellitus ,medicine ,Humans ,Cellular Senescence ,Telomere Shortening ,Glycated Hemoglobin ,TUNEL assay ,Infant, Newborn ,Obstetrics and Gynecology ,Telomere ,medicine.disease ,Senescence-associated heterochromatin focus ,Trophoblasts ,Diabetes, Gestational ,medicine.anatomical_structure ,Reproductive Medicine ,Case-Control Studies ,Cord blood ,Immunology ,Female ,Developmental Biology - Abstract
Introduction The intrauterine environment, including the placenta, is influenced by a variety of factors, among which is diabetes during pregnancy. These factors can affect lifetime morbidity. Senescence is a state of cellular metabolic arrest, known to be correlated with age-related diseases and is usually accompanied by short telomeres. This study evaluated telomere characteristics in placentas and in cord blood from term pregnancies complicated by uncontrolled diabetes mellitus. Methods Placental biopsies and cord blood were collected from 16 pregnancies with poorly controlled diabetes and from 16 healthy controls. Senescence-associated heterochromatin foci (SAHF) and senescence-associated β-galactosidase (SAβ-Gal) staining were evaluated. Apoptosis was evaluated using tunel staining. Telomere length and aggregate formation were assessed in placentas and in cord blood using Q-FISH. Results Increased SAHF (19.28% ± 7.93 vs. 7.78% ± 5.31, P
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- 2015
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44. Prediction of the efficacy of dinoprostone slow release vaginal insert (Propess) for cervical ripening: A prospective cohort study
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Yair, Daykan, Tal, Biron-Shental, Daniella, Navve, Netanella, Miller, Mor, Bustan, and Rivka, Sukenik-Halevy
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Adult ,Administration, Intravaginal ,Young Adult ,Pregnancy ,Delayed-Action Preparations ,Oxytocics ,Outcome Assessment, Health Care ,Humans ,Female ,Prospective Studies ,Dinoprostone ,Cervical Ripening - Abstract
To evaluate factors predictive of the success of dinoprostone slow release vaginal insert for cervical ripening.A total of 169 women who underwent cervical ripening with dinoprostone slow release vaginal insert were included in the study cohort. The correlation between parameters present before cervical ripening with dinoprostone slow release and its success, as well as complications and adverse outcomes were analyzed.Dinoprostone slow release vaginal insert was successful in achieving vaginal delivery in 148 of 169 (87.6%), while sufficient ripening was achieved in 140 (83%) cases. Factors associated with successful vaginal delivery were multiparity and younger gestational age at delivery. Factors predictive of the success of cervical ripening with dinoprostone slow release vaginal insert were lower body mass index (BMI), higher parity and perceived contractions prior to insertion. Intrauterine growth restriction was associated with a significant risk for dinoprostone insert removal. Neonatal outcomes were similar in cases of successful or failed ripening.The success of cervical ripening with dinoprostone slow release vaginal insert can be predicted by factors that can be recognized at admission.
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- 2017
45. The yield of the prenatal work-up in intrauterine growth restriction and the spectrum of fetal abnormalities detected postnatally
- Author
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Tal Biron-Shental, Adi Katz, Rivka Sukenik-Halevy, Reuven Sharony, Rivka Regev, Ofer Markovitch, and Yael Ganor Paz
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Adult ,medicine.medical_specialty ,Yield (finance) ,Intrauterine growth restriction ,Serology ,Retrospective data ,Congenital Abnormalities ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pregnancy ,030225 pediatrics ,medicine ,Humans ,Israel ,Retrospective Studies ,Fetus ,030219 obstetrics & reproductive medicine ,Fetal Growth Retardation ,Obstetrics ,business.industry ,Pregnancy Outcome ,Obstetrics and Gynecology ,medicine.disease ,Placental Insufficiency ,humanities ,Work-up ,body regions ,Pediatrics, Perinatology and Child Health ,Female ,business - Abstract
To evaluate the yield of work-up in intrauterine growth restriction (IUGR) pregnancies and their outcomes.Retrospective data regarding prenatal work-up (serology, genetic testing and imaging), and neonatal outcomes of 198 IUGR pregnancies (estimated fetal weight10th percentile) were analyzed.IUGR was isolated in 72 cases. Work-up performed in 158 (80%) cases was positive in 4 (2.5%). No abnormalities were detected in prenatal genetic testing. Echocardiogram performed in 27 cases was abnormal in 3 (11.1%). Serological testing performed in 150 pregnancies (75.8%) detected 1 case (0.7%) of cytomegalovirus (CMV) infection. Thirteen neonates (6.5%) were diagnosed with significant health problems. A positive work-up and significant postnatal health problems were not correlated with IUGR severity, symmetry or additional concurrent findings.The yield of IUGR work-up is not clear and is probably highest for fetal echocardiography. The rate of significant adverse outcomes after birth is increased in IUGR pregnancies.
- Published
- 2017
46. 389: The yield of Chromosomal microarray analysis in cases of pregnancy termination due to fetal malformations
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Tamar Tenne, Tal Biron-Shental, Yael Pasternak, Rivka Sukenik Halevy, Gil Shechter-Maor, Yair Daykan, Netanella Miller, Idit Maya, and Eyal Reinstein
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Andrology ,Fetus ,Microarray analysis techniques ,business.industry ,Yield (chemistry) ,Obstetrics and Gynecology ,Medicine ,Pregnancy termination ,business - Published
- 2019
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47. Telomere shortening in intra uterine growth restriction placentas
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Ido Laish, Moshe Fejgin, Aliza Amiel, Yudith Sharon, Tal Biron-Shental, and Rivka Sukenik-Halevy
- Subjects
Senescence ,Intrauterine growth restriction ,Biology ,Andrology ,chemistry.chemical_compound ,Telomere Homeostasis ,Placenta ,medicine ,Homeostasis ,Humans ,Telomerase reverse transcriptase ,DAPI ,In Situ Hybridization, Fluorescence ,Telomere Shortening ,reproductive and urinary physiology ,Fetal Growth Retardation ,Reverse Transcriptase Polymerase Chain Reaction ,Obstetrics and Gynecology ,medicine.disease ,Senescence-associated heterochromatin focus ,Molecular biology ,female genital diseases and pregnancy complications ,Telomere ,medicine.anatomical_structure ,chemistry ,Case-Control Studies ,embryonic structures ,Pediatrics, Perinatology and Child Health ,Female - Abstract
Placentas from pregnancies complicated with IUGR (intrauterine growth restriction) express altered telomere homeostasis. In the current study, we examined mechanisms of telomere shortening in these placentas.Placental biopsies from 15 IUGR and 15 healthy control pregnancies were examined. The percentage of trophoblasts with fragmented nuclei: senescence-associated heterochromatin foci (SAHF), was calculated using DAPI staining. The amount of human telomerase reverse transcriptase (hTERT) mRNA was evaluated using RtPCR levels of telomere capture using FISH in those samples were estimated.The percentage of trophoblasts with SAHF was higher in IUGR compared to control samples, (25±13.4% vs. 1.6±1.6%, P0.0001), hTERT mRNA was decreased (0.5±0.2 vs. 0.9±0.1, P0.0001) and telomere capture was increased (13.2±9.7% vs.1.3±2.5%, P0.001).We suggest that IUGR placentas express increased signs of senescence as part of the impaired telomere homeostasis. One factor that mediates telomere shortening in these placentas is decreased hTERT mRNA, leading to decreased protein expression and therefore, reduced telomere elongation. Telomere capture, which is a healing process, is increased in IUGR trophoblasts as a compensatory mechanism.
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- 2014
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48. Microscopic chromosome Xp distal deletions - a challenging issue in prenatal genetic counseling
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Myriam Goldstein, Avi Orr-Ortreger, Shay Ben-Shachar, Sharon Simchoni, Anat Bar-Shira, Yuval Yaron, Rivka Sukenik-Halevy, and Adi Reches
- Subjects
Genetics ,Genetic counseling ,Pseudoautosomal region ,Obstetrics and Gynecology ,Chromosome ,Prenatal diagnosis ,Karyotype ,Biology ,Short stature ,X-inactivation ,medicine ,medicine.symptom ,Genetics (clinical) ,X chromosome - Abstract
Objective A prenatal diagnosis of chromosome X short arm deletions may present a challenge in prenatal genetic counseling. We present clinical and molecular data of carriers of Xp distal deletions. Methods We assessed prenatal and postnatal phenotypes of individuals from three families with large Xp distal deletions and from a fourth family with a small Xp distal deletion. The work-up included karyotyping, chromosomal microarray analysis, and assessment of the X inactivation pattern. Results Five out of eight women with large deletions had a short stature (
- Published
- 2014
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49. The yield and complications of amniocentesis performed after 24 weeks of gestation
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Tal Biron-Shental, Ohad Ben-Zvi, Amir Peleg, Omer Weitzner, Keren Tzadikevitch Geffen, and Rivka Sukenik-Halevy
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Adult ,medicine.medical_specialty ,Pregnancy Trimester, Third ,Gestational Age ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Medicine ,Amniocyte ,Humans ,030212 general & internal medicine ,Genetic testing ,Retrospective Studies ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Obstetrics ,Medical record ,Pregnancy Outcome ,Obstetrics and Gynecology ,Gestational age ,Retrospective cohort study ,General Medicine ,medicine.disease ,Pregnancy Complications ,Pregnancy Trimester, Second ,Amniocentesis ,Gestation ,Female ,business ,Maternal Age - Abstract
This study assessed the use and complications of late amniocentesis (AC) and analyzed factors that affect complication rate. A retrospective analysis of 167 genetic AC performed after 24 weeks during a 10-year period in two medical centers was conducted. Data regarding the indications for AC, genetic work-up, and pregnancy outcomes were retrieved from patient medical records and telephone-based questionnaires. Mean gestational age (GA) at the time of AC was 31.7 ± 2.7 weeks; 104 procedures were performed at ≤32 weeks, including 24 at ≤30 weeks. The overall pregnancy complication rate occurring at any time after the procedure was 6.6% (11). Of these, 4.8% (8) occurred within a month after AC, including 2.4% (4) that occurred within a week. An additional three occurred after 30 days. There were no differences in the total complication rate and in the rate of specific complications of procedures performed at ≤32 weeks or at ≤30 weeks. Maternal age did not affect outcomes. Genetic testing was abnormal in five cases (3%). Amniocyte culture failed in 3 cases (2.3%), with no technical failures in 52 chromosomal microarray tests. The complication rate of AC performed after 24 weeks was 4.8%, which is significantly higher than that of second trimester AC. GA and maternal age did not affect the complication rate.
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- 2017
50. Clinical aspects of prenatally detected congenital heart malformations and the yield of chromosomal microarray analysis
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Rivka, Sukenik-Halevy, Shay, Sukenik, Arie, Koifman, Yoav, Alpert, Reli, Hershkovitz, Alex, Levi, and Tal, Biron-Shental
- Subjects
Adult ,Chromosome Aberrations ,Heart Defects, Congenital ,Karyotype ,Pregnancy Outcome ,Gestational Age ,Microarray Analysis ,Ultrasonography, Prenatal ,Pregnancy ,Prenatal Diagnosis ,Humans ,Female ,Genetic Testing ,Nuchal Translucency Measurement - Abstract
The yield of chromosomal microarray analysis (CMA) for prenatally detected congenital heart defects (CHD) is 6.6% to 19.2%. We evaluated the yield of CMA in cases of prenatally detected CHD in regard to specific clinical characteristics.Data from 192 cases of CHD including type, clinical and familial background, workup performed during the pregnancy, and pregnancy outcomes were collected.Fetal echocardiography was performed in all cases; 61.4% of CHD were suspected by ultrasound. There was a positive family history (FH) in 15.7%. Abnormal nuchal translucency or umbilical cord anomalies were detected in 1.7% and 5.9%, respectively, and 55.1% were isolated cases. In 11 of 96 cases in which genetic testing was performed, karyotype and CMA were abnormal (11.5%). The detection rate of CMA (performed in 72 cases) was 9.7%. The yield of CMA was similar in simple cases, isolated cases, and cases with a positive FH. CMA was abnormal in 7.3% of ventricular septal defect cases.Most cases of prenatally detected CHD had no additional extra-cardiac, sonographic findings suggesting increased risk for CHD. The yield of CMA testing was significant in all clinical scenarios including simple heart malformations, isolated cases, and cases with a positive FH. © 2016 John WileySons, Ltd.
- Published
- 2016
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