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1.
Medicine (Baltimore) ; 100(2): e24091, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33466173

RESUMO

RATIONALE: Partial trisomy of the long arm of chromosome 6 syndrome is a rare chromosomal disorder with distinctive phenotypic expressivity, in which cytogenetic abnormalities are usually reported in infancy and childhood. Ultrasonographic findings on trisomy of the distal long arm of chromosome 6 in previous studies are limited. PATIENT CONCERNS: A 32-year-old, gravida 6, para 1, pregnant woman who had 4 spontaneous abortions underwent a clinical ultrasound examination at 26 weeks of gestation. DIAGNOSES: Ultrasonographic findings were microcephaly, an acoustic image of a transparent septum, a flat nasal bridge, right pulmonary artery stenosis, and a single umbilical artery. Cytogenetic and single-nucleotide polymorphism array analyses were performed to estimate genetic factors of this diagnosis by amniocentesis. INTERVENTIONS: After genetic counseling, the patient and her husband opted to terminate the pregnancy. OUTCOMES: Cytogenetic examination of the fetus showed the karyotype 46,XX,der(20)t(6;20)(q24;p13). The single-nucleotide polymorphism (SNP) array showed a 22.104-Mb duplication of 6q24.3q27 and a 0.784-Mb deletion of 20p13. LESSONS: Ultrasonographic findings of fetal abnormalities, including microcephaly, an acoustic image of a transparent septum, a flat nasal bridge, right pulmonary artery stenosis, and a single umbilical artery, may be related to a 22.104-Mb duplication of 6q24.3q27 and a 0.784-Mb deletion of 20p13. More ultrasonographic and genotype studies are required to extend the phenotypic characterization of partial trisomy 6q syndrome.


Assuntos
Transtornos Cromossômicos/diagnóstico por imagem , Ultrassonografia Pré-Natal , Aborto Induzido , Adulto , Amniocentese , Transtornos Cromossômicos/embriologia , Cromossomos Humanos Par 6 , Feminino , Feto/diagnóstico por imagem , Humanos , Cariótipo , Polimorfismo de Nucleotídeo Único , Gravidez , Trissomia
3.
Artigo em Inglês | MEDLINE | ID: mdl-33321999

RESUMO

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4-BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers' cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting.


Assuntos
Variações do Número de Cópias de DNA , Transtornos Mentais/genética , Transtornos do Neurodesenvolvimento/genética , Deleção Cromossômica , Transtornos Cromossômicos/genética , Duplicação Cromossômica , Cromossomos Humanos Par 16/genética , Heterozigoto , Humanos
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1276-1279, 2020 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-33179239

RESUMO

OBJECTIVE: To carry out prenatal diagnosis for a fetus with Pallister-killian syndrome (PKS). METHODS: The fetus was found to have limb malformations at 23rd gestational week. With informed consent from its parents, amniotic fluid sample was taken from the fetus and subjected to chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) assay. RESULTS: G-banding analysis suggested the fetus has a mos47,XY,+mar[55]/46,XY[10] karyotype. CMA analysis of the cultured amniocytes with CytoScan 750K microarray revealed a segmental tetrasomy duplication of 12p13.33p11.1. FISH confirmed a 70% mosaicism of tetrasomy 12p in the metaphase amniocytes with 12pter/12qter probes. CONCLUSION: Combined use of G-banding karyotyping, CMA and FISH analysis has enabled diagnosis of PKS in the fetus. Although short limb is a common feature of PKS, unequal femur length has not been reported previously, which has expanded the spectrum of PKS-associated limb abnormalities.


Assuntos
Transtornos Cromossômicos/diagnóstico , Diagnóstico Pré-Natal , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 12/genética , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Mosaicismo , Gravidez
5.
Zhonghua Fu Chan Ke Za Zhi ; 55(10): 679-684, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33120479

RESUMO

Objective: To explore the clinical application value and accuracy of cell-free fetal DNA (cff-DNA) technique in prenatal screening. Methods: The results of quantitative fluorescent PCR (QF-PCR) and karyotype of amniotic fluid cells were analyzed retrospectively in 2 398 monocyesis pregnant women who had been amniocentesis at the First Affiliated Hospital of Zhengzhou University from May 2013 to December 2019, and the results of 359 cases who had been examined by single-nucleotide polymorphism array (SNP array). Results: Cff-DNA test of 2, 398 cases indicated 987 cases of trisomy 21, 351 cases of trisomy 18, 135 cases of trisomy 13, 566 cases of sex chromosome abnormality, and 359 cases of other chromosome abnormality. Chromosome karyotype analysis detected 826 cases of trisomy 21, 213 cases of trisomy 18, 17 cases of trisomy 13, 221 cases of sex chromosome abnormality, and 26 cases of other chromosome abnormality. The detection rate were 83.69% (826/987), 60.68% (213/351), 12.59% (17/135), 39.04% (221/566) and 7.24% (26/359), respectively. QF-PCR detected 1 046 cases of trisomy and 188 cases of sex chromosomes abnormality, and the detection rate was 99.05% (1 046/1 056) and 85.07% (188/221), respectively. Compared with the abnormal number detected by chromosome karyotype analysis, 10 cases of trisomeric chimerism and 24 cases of sex chromosome were missed by QF-PCR. Among the 359 other chromosomal abnormalities detected by SNP array, 64 cases were consistent with the results of cff-DNA, and the detection rate was 17.83% (64/359), which was 10.59% higher than the karyotype result. Conclusions: Karyotype analysis is the gold standard for diagnosing chromosomal abnormalities. QF-PCR could diagnose common chromosome aneuploidy rapidly and accurately, and it could be used as an auxiliary detection technique for karyotype analysis. The incidence of sex chromosome chimerism is high, so missed diagnosis should be warned. SNP array could be given priority to verify chromosome microdeletion or microduplication detected by cff-DNA.


Assuntos
Ácidos Nucleicos Livres/genética , Transtornos Cromossômicos/diagnóstico , Doenças Fetais/diagnóstico , Diagnóstico Pré-Natal/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Trissomia/genética , Aneuploidia , Transtornos Cromossômicos/genética , DNA/genética , Feminino , Doenças Fetais/sangue , Doenças Fetais/genética , Humanos , Gravidez , Estudos Retrospectivos , Trissomia/diagnóstico
6.
Obstet Gynecol ; 136(4): 859-867, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32976375

RESUMO

Prenatal testing for chromosomal abnormalities is designed to provide an accurate assessment of a patient's risk of carrying a fetus with a chromosomal disorder. A wide variety of prenatal screening and diagnostic tests are available; each offers varying levels of information and performance, and each has relative advantages and limitations. When considering screening test characteristics, no one test is superior in all circumstances, which results in the need for nuanced, patient-centered counseling from the obstetric care professional and complex decision making by the patient. Each patient should be counseled in each pregnancy about options for testing for fetal chromosomal abnormalities. It is important that obstetric care professionals be prepared to discuss not only the risk of fetal chromosomal abnormalities but also the relative benefits and limitations of the available screening and diagnostic tests. Testing for chromosomal abnormalities should be an informed patient choice based on provision of adequate and accurate information, the patient's clinical context, accessible health care resources, values, interests, and goals. All patients should be offered both screening and diagnostic tests, and all patients have the right to accept or decline testing after counseling.The purpose of this Practice Bulletin is to provide current information regarding the available screening test options available for fetal chromosomal abnormalities and to review their benefits, performance characteristics, and limitations. For information regarding prenatal diagnostic testing for genetic disorders, refer to Practice Bulletin No. 162, Prenatal Diagnostic Testing for Genetic Disorders. For additional information regarding counseling about genetic testing and communicating test results, refer to Committee Opinion No. 693, Counseling About Genetic Testing and Communication of Genetic Test Results. For information regarding carrier screening for genetic conditions, refer to Committee Opinion No. 690, Carrier Screening in the Age of Genomic Medicine, and Committee Opinion No. 691, Carrier Screening for Genetic Conditions. This Practice Bulletin has been revised to further clarify methods of screening for fetal chromosomal abnormalities, including expanded information regarding the use of cell-free DNA in all patients regardless of maternal age or baseline risk, and to add guidance related to patient counseling.


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos , Aconselhamento , Doenças Fetais , Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Aconselhamento/métodos , Aconselhamento/normas , Aconselhamento/provisão & distribução , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Acesso aos Serviços de Saúde/normas , Humanos , Assistência Centrada no Paciente/métodos , Assistência Centrada no Paciente/normas , Guias de Prática Clínica como Assunto , Gravidez , Estados Unidos
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1065-1068, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924102

RESUMO

OBJECTIVE: To review the results of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), numerical aberration of sex and other autosomes and copy number variations with a size of >5 Mb. METHODS: NIPT was carried out for 44 578 pregnant women. For those with a high-risk by NIPT, amniotic fluid or cord blood samples were collected for G-banding karyotype analysis, and the pregnancy outcome was followed up. RESULTS: Among the 44 578 pregnant women, 466 (1.05%) were diagnosed as high risk of T21 (n = 1359), T18 (n = 178) or T13 (n = 129). Among these, 301, 53 and 20 were subjected to prenatal diagnosis by amniocyte or umbilical blood karyotyping analysis, among which 289 were diagnosed as T21, 40 (75.47%) as T18, and 4 (20.00%) as T13. Among the high-risk pregnant women, 2 cases were diagnosed as Down syndrome after birth, while no trisomy 18 and trisomy 13 were recorded. The sensitivity and specificity of NIPT were T21 (99.31%, 99.97%), T18 (100%, 99.97%), T13 (100%, 99.96%), respectively. The positive predictive values for T21, T18 and T13 by NIPT were 96.01%, 75.47% and 20.00%, respectively. CONCLUSION: Compared with conventional serological screening and invasive prenatal diagnosis, NIPT has a high sensitivity and specificity for T21, T18 and T13, and has provided an ideal method to screen fetal chromosomal abnormalities.


Assuntos
Transtornos Cromossômicos , Diagnóstico Pré-Natal/métodos , Líquido Amniótico/citologia , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Variações do Número de Cópias de DNA , Feminino , Sangue Fetal , Humanos , Cariotipagem , Gravidez , Estudos Retrospectivos , Sensibilidade e Especificidade , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/genética
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1084-1086, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924106

RESUMO

OBJECTIVE: To carry out prenatal diagnosis on a fetus with abnormal findings by ultrasonography and non-invasive prenatal testing. METHODS: The fetus and both parents were subjected to chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) analysis. RESULTS: The karyotypes of both parents were normal. The fetus carried a 46,N,der(X;16)(q28;q22) unbalanced translocation. SNP-array analysis confirmed that the derived chromosomal fragment of the fetus has originated from 16q. The fetus was diagnosed with 16q partial trisomy syndrome. CONCLUSION: Combined chromosomal karyotyping analysis and SNP-array can detect chromosomal aberrations at submicroscopic level and enable accurate diagnosis of the fetus.


Assuntos
Transtornos Cromossômicos , Diagnóstico Pré-Natal/métodos , Trissomia , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 16 , Feminino , Feto , Humanos , Cariotipagem , Gravidez , Trissomia/diagnóstico , Trissomia/genética , Ultrassonografia
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1117-1119, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924114

RESUMO

OBJECTIVE: To explore the value of in situ amniocyte culture for prenatal diagnosis. METHODS: 2716 amniotic fluid samples were cultured in situ on slides. After the culture, the slides were stained, photographed and analyzed. RESULTS: All samples were successfully analyzed, with the success rates for primary culture and subculture being 98.42% and 1.58%, respectively. 224 samples (8.25%) were detected with chromosomal aberrations, which included 125 cases with trisomy 21, 31 with trisomy 18, 3 with trisomy 13, 4 with 45,X, 17 with 47,XXY, 5 with 47,XYY, 1 with 48,XXY,+18, 1 with 48,XXYY, 26 with structural chromosomal aberrations, and 11 with mosaicisms for aneuploidies. CONCLUSION: In situ amniocyte culture is stable and has a high success rate, and is capable of identifying true and false mosaicisms, which can improve the accuracy of prenatal diagnosis.


Assuntos
Líquido Amniótico/citologia , Aberrações Cromossômicas , Transtornos Cromossômicos , Diagnóstico Pré-Natal , Aneuploidia , Transtornos Cromossômicos/diagnóstico , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Gravidez , Trissomia
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1167-1171, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924127

RESUMO

OBJECTIVE: To delineate chromosomal aberration caused by structural chromosomal abnormalities with bionano optical mapping. METHODS: Chromosomal karyotyping, bionano optical mapping and copy number variation sequencing (CNV-seq) were used to delineate the chromosomal aberration carried by a patient. RESULTS: The patient was found to have an anomalous chromosome 16 by karyotyping analysis, which was verified by bionano optical mapping and CNV-seq as loss of heterozygosity at 16p11.2-p12.2. CONCLUSION: Bionano optical mapping has provided a novel tool for the detection and diagnosis of structural chromosomal aberrations.


Assuntos
Deleção Cromossômica , Transtornos Cromossômicos , Variações do Número de Cópias de DNA , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 16 , Humanos , Cariotipagem
11.
Rev. neurol. (Ed. impr.) ; 71(5): 171-176, 1 sept., 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-195467

RESUMO

INTRODUCCIÓN: El retraso general del desarrollo (RGD) constituye un trastorno intelectual y del comportamiento adaptativo que aparece en los niños menores de 5 años que no consiguen alcanzar los hitos del desarrollo normal. La discapacidad intelectual se caracteriza por la limitación en el funcionamiento intelectual y en el comportamiento adaptativo, surgida en la infancia. Entre las causas frecuentes y reconocibles del RGD y de la discapacidad intelectual se encuentran los desequilibrios cromosómicos. Los arrays de hibridación genómica comparada (aCGH) han contribuido a mejorar la tasa de detección de las anomalías genéticas y ya se consideran la prueba genética de elección para la discapacidad intelectual de origen desconocido. OBJETIVO: Analizar los resultados del estudio genético con aCGH motivado por un RGD o una discapacidad intelectual en pacientes pediátricos. PACIENTES Y MÉTODOS: Análisis retrospectivo de pacientes pediátricos sometidos a seguimiento ambulatorio que fueron objeto de un estudio genético con aCGH entre 2012 y 2017. RESULTADOS: El número de pacientes sometidos al estudio con aCGH ascendió a 215. Del total, el 64,2% fueron investigados por discapacidad intelectual, y el 35,8%, por RGD. El 23,3% presentó deleciones o duplicaciones en la aCGH; el 56%, por la discapacidad intelectual; y el 44%, por el RGD, y los cromosomas 16, 22, 2 y 1 fueron los implicados con más frecuencia. CONCLUSIÓN: El presente estudio demuestra la mayor prevalencia de ambos en el sexo masculino, en consonancia con otras publicaciones precedentes. La tasa de detección de las anomalías clasificadas como patógenas resultó superior a la notificada en otros estudios


INTRODUCTION: Global developmental delay (GDD) is an intellectual and adaptive impairment in infants under 5 years of age who fail to meet expected developmental milestones. Intellectual disability is characterized by limitation in intellectual function and adaptive behavior, with onset in childhood. Frequent identifiable causes of GDD and intellectual disability are chromosomal imbalances. The array comparative genomic hybridization (aCGH) has contributed to improve the detection rate of genetic abnormalities and is considered the first-tier genetic test for unexplained intellectual disability. AIM: To analyze the results of a genetic study by aCGH due to GDD or intellectual disability in pediatric patients. PATIENTS AND METHODS: Retrospective analysis of pediatric patients followed in outpatient, which underwent a genetic study by aCGH, from 2012 to 2017. RESULTS: 215 patients were studied by aCGH. Of the total, 64.2% were investigated for intellectual disability and 35.8% for GDD. A 23.3% presented aCGH deletions or duplications, 56% for intellectual disability and 44% for GDD, with chromosomes 16, 22, 2 and 1 being the most implicated. CONCLUSION: Our study demonstrated a higher prevalence in males, according to previously published reports. The rate of detection abnormalities classified as pathogenic was higher than in other studies


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/genética , Transtornos Cromossômicos/diagnóstico , Deficiência Intelectual/genética , Transtornos Cromossômicos/genética , Estudos Retrospectivos , Deleção de Genes
12.
PLoS One ; 15(8): e0238245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845907

RESUMO

To study the detection limits of chromosomal microaberrations in non-invasive prenatal testing with aim for five target microdeletion syndromes, including DiGeorge, Prader-Willi/Angelman, 1p36, Cri-Du-Chat, and Wolf-Hirschhorn syndromes. We used known cases of pathogenic deletions from ISCA database to specifically define regions critical for the target syndromes. Our approach to detect microdeletions, from whole genome sequencing data, is based on sample normalization and read counting for individual bins. We performed both an in-silico study using artificially created data sets and a laboratory test on mixed DNA samples, with known microdeletions, to assess the sensitivity of prediction for varying fetal fractions, deletion lengths, and sequencing read counts. The in-silico study showed sensitivity of 79.3% for 10% fetal fraction with 20M read count, which further increased to 98.4% if we searched only for deletions longer than 3Mb. The test on laboratory-prepared mixed samples was in agreement with in-silico results, while we were able to correctly detect 24 out of 29 control samples. Our results suggest that it is possible to incorporate microaberration detection into basic NIPT as part of the offered screening/diagnostics procedure, however, accuracy and reliability depends on several specific factors.


Assuntos
Mapeamento Cromossômico/métodos , Limite de Detecção , Teste Pré-Natal não Invasivo/métodos , Sequenciamento Completo do Genoma/métodos , Ácidos Nucleicos Livres/análise , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 1/genética , Síndrome do Miado do Gato/diagnóstico , Síndrome do Miado do Gato/genética , Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Feminino , Humanos , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Gravidez , Cuidado Pré-Natal , Síndrome de Wolf-Hirschhorn/diagnóstico , Síndrome de Wolf-Hirschhorn/genética
13.
Obstet Gynecol ; 136(4): e48-e69, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32804883

RESUMO

Prenatal testing for chromosomal abnormalities is designed to provide an accurate assessment of a patient's risk of carrying a fetus with a chromosomal disorder. A wide variety of prenatal screening and diagnostic tests are available; each offers varying levels of information and performance, and each has relative advantages and limitations. When considering screening test characteristics, no one test is superior in all circumstances, which results in the need for nuanced, patient-centered counseling from the obstetric care professional and complex decision making by the patient. Each patient should be counseled in each pregnancy about options for testing for fetal chromosomal abnormalities. It is important that obstetric care professionals be prepared to discuss not only the risk of fetal chromosomal abnormalities but also the relative benefits and limitations of the available screening and diagnostic tests. Testing for chromosomal abnormalities should be an informed patient choice based on provision of adequate and accurate information, the patient's clinical context, accessible health care resources, values, interests, and goals. All patients should be offered both screening and diagnostic tests, and all patients have the right to accept or decline testing after counseling.The purpose of this Practice Bulletin is to provide current information regarding the available screening test options available for fetal chromosomal abnormalities and to review their benefits, performance characteristics, and limitations. For information regarding prenatal diagnostic testing for genetic disorders, refer to Practice Bulletin No. 162, Prenatal Diagnostic Testing for Genetic Disorders. For additional information regarding counseling about genetic testing and communicating test results, refer to Committee Opinion No. 693, Counseling About Genetic Testing and Communication of Genetic Test Results. For information regarding carrier screening for genetic conditions, refer to Committee Opinion No. 690, Carrier Screening in the Age of Genomic Medicine and Committee Opinion No. 691, Carrier Screening for Genetic Conditions. This Practice Bulletin has been revised to further clarify methods of screening for fetal chromosomal abnormalities, including expanded information regarding the use of cell-free DNA in all patients regardless of maternal age or baseline risk, and to add guidance related to patient counseling.


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos , Aconselhamento , Doenças Fetais , Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Aconselhamento/métodos , Aconselhamento/normas , Aconselhamento/provisão & distribução , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Acesso aos Serviços de Saúde/normas , Humanos , Assistência Centrada no Paciente/métodos , Assistência Centrada no Paciente/normas , Gravidez , Estados Unidos
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 843-846, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761591

RESUMO

OBJECTIVE: To explore the genetic basis for a child featuring short stature. METHODS: G-banded karyotyping, chromosomal microarray analysis (CMA) and high-throughput sequencing were carried out on peripheral blood sample from the child. RESULTS: The karyotype of the child was ascertained as 45,XY,-4[3]/46,XY,r(4)(p16q35)[84]/47,XY,-4,r(4)(p16q25)*2[7]/48,XY,-4,r(4)(p16q35)*3[1]/46,XY,dic r(4;4)(p16q35;p16q35)[2]/46,XY,add(4)(p16)[3]. A 647 kb deletion at 4p16.3 was identified by CMA, which encompassed 6 OMIM genes including ZNF141, PIGG, PDE6B, ATP5I, PCGF3 and MYL5. High-throughput sequencing has identified no pathogenic/likely pathogenic variants consistent with the clinical symptoms. CONCLUSION: A rare ring chromosome 4 syndrome was identified by combined chromosomal karyotyping, CMA and high-throughput sequencing. Conventional cytogenetic analysis and genetic testing in combine have enabled the diagnosis in this case.


Assuntos
Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cariotipagem , Criança , Bandeamento Cromossômico , Cromossomos Humanos Par 4/genética , Humanos , Cromossomos em Anel
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 879-882, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761600

RESUMO

OBJECTIVE: To diagnose a 46,XN,del(11)(q14q22) fetus by non-invasive prenatal testing (NIPT), karyotype analysis and whole genome sequencing (WGS). METHODS: Peripheral blood sample of the gravida was taken for NIPT screening. Blood samples of the gravida, her husband, and umbilical cord blood were also taken for chromosome karyotyping and whole genome sequencing (WGS). RESULTS: NIPT screening indicated the fetus has carried partial deletion of chromosome 11, while no chromosomal abnormality was found with the cord blood sample due to the low resolution of G-banding analysis. WGS analysis of the cord blood indicated 46,XN,del(11q14.3q22.1). seq[GRCh37/hg19] (90 623 404-97 469 319)×1, 6.85 Mb. The karyotype of the fetus was eventually determined as 46,XN,del(11)(q14q22). Karyotyping analysis suggested that the gravida and her husband were 46,XX,del(11)(q14q22)[8]/46,XX[92] and 46,XY, respectively. However, neither of them was found to harbor the del(11)(q14q22) by WGS. CONCLUSION: The abnormal karyotype of the fetus has derived from its mother's low percentage mosaicism. Combined NIPT, karyotyping analysis and WGS can detect chromosomal disorders with accuracy.


Assuntos
Transtornos Cromossômicos , Diagnóstico Pré-Natal , Transtornos Cromossômicos/genética , Feminino , Feto , Testes Genéticos , Humanos , Cariotipagem , Gravidez
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 891-894, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761603

RESUMO

OBJECTIVE: To explore the value of BACs-on-BeadsTM (BoBs) for the practice of prenatal diagnosis. METHODS: The results of chromosomal karyotyping and BoBs of 1773 prenatal samples were compared. Microdeletions and microduplications detected by BoBs were subjected to chromosome microarray analysis (CMA) with informed consent from patients. RESULTS: BoBs has detected 46 cases of common aneuploidies involving chromosomes 13, 18, and 21, and 16 cases involving X and Y chromosomes. For 4 fetuses with normal results by BoBs, karyotyping analysis of amniotic fluid sample suggested low percentage mosaicisms (< 20%). BoBs has detected none of the 9 common microdeletions, but 14 male fetuses with Xp22 microdeletions and 5 with other microdeletions/microduplications. In 10 cases, the couples had chosen CMA verification, and the results were all consistent. CONCLUSION: As a rapid diagnostic technique, BoBs has a high accuracy for common aneuploidies, and is capable of discovering certain chromosome microdeletions and microduplications. The difficulty lies in the inability to detect low proportion mosaicisms and the consultation following detection for male fetuses carrying Xp22 microdeletions.


Assuntos
Transtornos Cromossômicos , Diagnóstico Pré-Natal/métodos , Aneuploidia , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Artificiais Bacterianos , Feminino , Humanos , Cariotipagem , Masculino , Gravidez
17.
Nat Neurosci ; 23(9): 1090-1101, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32661394

RESUMO

While the neuronal underpinnings of autism spectrum disorder (ASD) are being unraveled, vascular contributions to ASD remain elusive. Here, we investigated postnatal cerebrovascular development in the 16p11.2df/+ mouse model of 16p11.2 deletion ASD syndrome. We discover that 16p11.2 hemizygosity leads to male-specific, endothelium-dependent structural and functional neurovascular abnormalities. In 16p11.2df/+ mice, endothelial dysfunction results in impaired cerebral angiogenesis at postnatal day 14, and in altered neurovascular coupling and cerebrovascular reactivity at postnatal day 50. Moreover, we show that there is defective angiogenesis in primary 16p11.2df/+ mouse brain endothelial cells and in induced-pluripotent-stem-cell-derived endothelial cells from human carriers of the 16p11.2 deletion. Finally, we find that mice with an endothelium-specific 16p11.2 deletion (16p11.2ΔEC) partially recapitulate some of the behavioral changes seen in 16p11.2 syndrome, specifically hyperactivity and impaired motor learning. By showing that developmental 16p11.2 haploinsufficiency from endothelial cells results in neurovascular and behavioral changes in adults, our results point to a potential role for endothelial impairment in ASD.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Células Endoteliais/patologia , Acoplamento Neurovascular/fisiologia , Animais , Transtorno Autístico , Circulação Cerebrovascular/fisiologia , Deleção Cromossômica , Transtornos Cromossômicos , Cromossomos Humanos Par 16 , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Feminino , Deficiência Intelectual , Masculino , Camundongos , Neovascularização Fisiológica/genética
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(7): 771-773, 2020 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-32619262

RESUMO

OBJECTIVE: To carry out G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA) for a fetus featuring multiple malformations. METHODS: The fetus was found to have increased nuchal thickness, generalized edema, asymmetric lower limbs, tetralogy of Fallot, nasal bone anomaly and cleft palate. Following amniocentesis, G-band karyotyping and CMA were carried out. RESULTS: The fetus had a karyotype of 47,XX,+i(12)(p10) [14]/46,XX[6]. CMA has identified a 33.9 Mb duplication at 12p13.33-p11.1, which was suggestive of tetrasomy 12p. CONCLUSION: Combined chromosomal karyotyping and CMA can delineate the origin of abnormal chromosomal fragments during prenatal diagnosis. The fetus was diagnosed with Pallister-Killian syndrome.


Assuntos
Transtornos Cromossômicos , Diagnóstico Pré-Natal , Amniocentese , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 12/genética , Feminino , Humanos , Cariotipagem , Gravidez
19.
Niger J Clin Pract ; 23(6): 864-869, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32525124

RESUMO

Background: An important component of the first-trimester scan is nuchal translucency thickness at 11 weeks to 13 weeks 6 days of gestation. A nuchal translucency ≥3.3 mm is a significant early pregnancy scan finding associated with Trisomies 13, 18, and 21 and congenital heart diseases. Aims: To determine the prevalence and outcome of increased fetal nuchal translucency among pregnant women. Subjects and Methods: A prospective cohort study at the Obstetrics and Gynaecology Department of Usmanu Danfodiyo University Teaching Hospital Sokoto. This was a prospective study of 265 consecutively recruited women in the first trimester of pregnancy who presented to antenatal clinics over a 20-week period. An NT scan was conducted at 11 weeks to 13 weeks 6 days followed by an anomaly scan at 18-22 weeks. Patients were followed up to delivery and 6-week post-partum. The neonates were examined at delivery and at 6-week postnatal life. Data entry and analysis was done with IBM SPSS version 20. The level of significance was set at less than 0.05. Frequency distribution; student t-test and Chi-squared test. Results: The 95th percentile NT was 3.3 mm and the prevalence of increased NT above 3.3 mm was 3%. The mean maternal age of the participants was 28.1 ± 5.1 years and the modal parity was Para 0. The most common anomalies associated with increased NT were ventricular septal defect and spina bifida. A congenital anomaly was significantly associated with increased NT (P < 0.001). Conclusions: The prevalence of increased fetal nuchal translucency is relatively high in our environment and is associated with congenital fetal defects. Routine screening with first-trimester ultrasound will help detect congenital anomalies early.


Assuntos
Transtornos Cromossômicos/diagnóstico por imagem , Feto/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Medição da Translucência Nucal/estatística & dados numéricos , Adulto , Aberrações Cromossômicas , Estudos de Coortes , Feminino , Idade Gestacional , Cardiopatias Congênitas , Hospitais de Ensino , Humanos , Recém-Nascido , Idade Materna , Nigéria/epidemiologia , Medição da Translucência Nucal/métodos , Gravidez , Primeiro Trimestre da Gravidez , Prevalência , Estudos Prospectivos , Ultrassonografia Pré-Natal , Adulto Jovem
20.
Hum Genet ; 139(11): 1417-1427, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32488466

RESUMO

An inverted duplication with a terminal deletion (inv-dup-del) is one of the complex constitutional structural rearrangements that can occur in a chromosome. Although breakages of dicentric chromosome have been suggested, the precise mechanism of this is yet to be fully understood. In our present study, we investigated the genomic structure of 10 inv-dup-del cases to elucidate this mechanism. Two recurrent 8p inv-dup-del cases harbored a large copy-number-neutral region between the duplication and deletion in common. Although the other non-recurrent cases did not appear to have this copy-number-neutral region, refined sequencing analysis identified that they contained a small intervening region at the junction between the inverted and non-inverted segment. The size of this small intervening region ranged from 1741 to 3728 bp. Combined with a presence of microhomology at the junction, a resolution of the replication fork stalling through template switching within the same replication fork is suggested. We further observed two cases with mosaicism of the dicentric chromosome and various structural rearrangements related to the dicentric chromosome. Refined analysis allowed us to identify different breakpoints on the same chromosome in the same case, implicating multiple rounds of U-type formation and its breakage. From these results, we propose that a replication-based mechanism generates unstable dicentric chromosomes and that their breakage leads to the formation of inv-dup-dels and other related derivative chromosomes.


Assuntos
Transtornos Cromossômicos/genética , Inversão Cromossômica/genética , Cromossomos/genética , Duplicação Gênica/genética , Deleção de Sequência/genética , Deleção Cromossômica , Replicação do DNA/genética , Humanos , Mosaicismo
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