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1.
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
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1061-1064, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924101

RESUMO

OBJECTIVE: To assess the performance of non-invasive prenatal testing (NIPT) for the detection of fetal chromosomal aneuploidies and its value for the prevention of birth defects. METHODS: In total 28 033 pregnant women underwent NIPT test. The results were compared with that of amniotic fluid and cord blood chromosomal karyotyping analysis. A few cases were verified by array comparative genome hybridization (aCGH). All pregnant women and their fetuses were followed up until after birth. RESULTS: NIPT has indicated a high risk for fetal chromosomal aneuploidies in 186 cases (0.66%), among which 101 (67.33%) were confirmed as 21, 18 and 13 trisomies by invasive prenatal diagnosis, which yielded a diagnostic rate of 86.52%, 50.00% and 19.05%, respectively. The diagnostic rates were 81.28%, 67.85%, 62.79% and 76.00% respectively for those ≥40, ≥35, 25 to 34, and <25. And the diagnostic rates were 65.91%, 60.78%, 71.79% and 80.00% for those over 35, with high risk by prenatal screening, critical risk by prenatal screening and ultrasound abnormality, respectively. CONCLUSION: The NIPT is effective for screening common chromosomal aneuploidies and preventing births of neonates with trisomy 21, trisomy 18 and trisomy 13.


Assuntos
Diagnóstico Pré-Natal/métodos , Trissomia/diagnóstico , Aneuploidia , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Humanos , Recém-Nascido , Cariotipagem , Gravidez , 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
3.
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
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1074-1078, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924104

RESUMO

OBJECTIVE: To retrospectively analyze non-invasive prenatal screening (NIPS) data from two centers. METHODS: The NIPS results of 10 840 samples were analyzed, including 21/18/13 trisomies (T21/T18/T13), sex chromosome and other autosomal aneuploidies, and copy number variants (CNVs). The maternal age, gestational week, body mass index and concentration of free fetal DNA (cffDNA) were also analyzed. RESULTS: The average gestational age of the 10 840 pregnant women was (32.34±5.04) year old, and the average gestational week for NIPS was (17.60±3.55) week. The overall false positive rate for T21/T18/T13 was 0.11%, sensitivity was 100%, specificity was 99.89%, and positive predictive value was 81.5%. The positive predictive values for sex chromosome and other autosomal aneuploidies and CNVs were 56.67%, 11.76% and 83.33%, respectively. The incidence of T21/T18 in the elder women (35 years or elder) was 2.12 times(P<0.01) and 1.81 times (P> 0.05) that of young women. cffDNA was in proportion to gestational week (r = 0.207) and in inverse proportion to body mass index (r = -0.177). It has increased slowly before 15 weeks of gestation and thereafter at a rate of 0.5% per week after the 16th week. CONCLUSION: The performance of NIPS in this study is by large close to the reported in the literature, and the results can provide a reference for further study.


Assuntos
Diagnóstico Pré-Natal/métodos , Trissomia , Adulto , Mineração de Dados , Feminino , Humanos , Idade Materna , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Sensibilidade e Especificidade , Trissomia/diagnóstico , Trissomia/genética
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1079-1083, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924105

RESUMO

OBJECTIVE: To carry out prenatal diagnosis for a fetus with high risk predicted by non-invasive prenatal testing (NIPT). METHODS: Next-generation sequencing (NGS) was used to analyze free fetal DNA (ffDNA) in the maternal plasma. Chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) were used to ascertain copy number variation in the fetus and its parents. RESULTS: SNP-array analysis and chromosomal karyotyping revealed that the fetus had a 15.018 Mb duplication at 4q34.1q35.2 and a 7.678 Mb duplication at 21q11.2q21.1, which were derived from a t(4;21)(q34.1;q21.1) translocation carried by its mother. CONCLUSION: NIPT is capable of detecting submicroscopic chromosomal abnormalities of the fetus. Combined use of genetic techniques, in particular SNP-array, is crucial for the diagnosis of partial trisomy 21q in this case.


Assuntos
Diagnóstico Pré-Natal/métodos , Trissomia , Ácidos Nucleicos Livres/sangue , Variações do Número de Cópias de DNA , Feminino , Feto , Testes Genéticos , Humanos , Cariotipagem , Polimorfismo de Nucleotídeo Único , Gravidez , Trissomia/diagnóstico , Trissomia/genética
6.
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
7.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1172-1175, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924128

RESUMO

OBJECTIVE: To explore the nature of chromosomal abnormality in a fetus with nasal bone dysplasia and clarify its clinical effect. METHODS: Fetal chromosome karyotype was analyzed by G-banding. Single nucleotide polymorphism array (SNP-array) was used to detect the chromosomal copy number variations, and fluorescence in situ hybridization (FISH) was used to verify the result. RESULTS: Fetal karyotype analysis showed an unknown chromosomal fragment in 21q21 region. SNP-array discovered a 7.5 Mb duplication in the 21q22.12q22.3 region. FISH confirmed that the unknown fragment was derived from a 21q22.12q22.3 duplication. CONCLUSION: Combined use of karyotype analysis, SNP-array and FISH has clarified the nature of chromosomal abnormality in a fetus with nasal bone dysplasia, which has enabled more accurate prenatal diagnosis and genetic counseling.


Assuntos
Doenças do Desenvolvimento Ósseo/genética , Diagnóstico Pré-Natal , Trissomia , Doenças do Desenvolvimento Ósseo/diagnóstico , Cromossomos Humanos Par 21 , Variações do Número de Cópias de DNA , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Polimorfismo de Nucleotídeo Único , Gravidez , Trissomia/diagnóstico , Trissomia/genética
8.
Scand J Immunol ; 92(5): e12973, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889730

RESUMO

Behçet's disease (BD) is a heterogeneous multi-organ disorder in search of a unified pathophysiological theory and classification. The disease frequently has overlapping features resembling other disease clusters, such as vasculitides, spondyloarthritides and thrombophilias with similar genetic risk variants, namely HLA-B*51, ERAP1, IL-10, IL-23R. Many of the BD manifestations, such as unprovoked recurrent episodes of inflammation and increased expression of IL-1, IL-6 and TNFα, overlap with those of the hereditary monogenic autoinflammatory syndromes, positioning BD at the crossroads between autoimmune and autoinflammatory syndromes. BD-like disease associates with various inborn errors of immunity, including familial Mediterranean fever, conditions related to dysregulated NF-κB activation (eg TNFAIP3, NFKB1, OTULIN, RELA, IKBKG) and either constitutional trisomy 8 or acquired trisomy 8 in myelodysplastic syndromes. We review here the recent advances in the immunopathology of BD, BD-like diseases and the NF-κB pathway suggesting new elements in the elusive BD etiopathogenesis.


Assuntos
Síndrome de Behçet/imunologia , Cromossomos Humanos Par 8/imunologia , NF-kappa B/imunologia , Trissomia/imunologia , Síndrome de Behçet/genética , Síndrome de Behçet/patologia , Cromossomos Humanos Par 8/genética , Predisposição Genética para Doença/genética , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Mucosa Bucal/imunologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Fenótipo , Úlcera Cutânea/genética , Úlcera Cutânea/imunologia , Úlcera Cutânea/patologia , Trissomia/genética
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(9): 1032-1035, 2020 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-32820524

RESUMO

OBJECTIVE: To determine the size and origin of a small supernumerary marker chromosome (sSMC) identified in a patient featuring developmental retardation. METHODS: High-throughput sequencing for copy number variation (CNV-seq) was carried out to delineate the sSMC identified upon G-banded chromosomal karyotyping. The genotype-phenotype correlation was explored by database retrieval and literature analysis. RESULTS: The patient was found to have a karyotype of mos 47,XX,+mar[36]/46,XX[23]. CNV-seq has identified a 18 Mb duplication at 5p14.1-p12 (hg19: 27,399,261-46,083,784)x2.6 with a mosaicism rate of approximately 60%. CONCLUSION: Patients with mosaic partial trisomy 5p may have extensive clinical manifestations, and the ratio of trisomy 5p cells is correlated with clinical severity of this syndrome.


Assuntos
Síndrome do Miado do Gato , Mosaicismo , Trissomia , Cromossomos Humanos Par 5 , Síndrome do Miado do Gato/diagnóstico , Síndrome do Miado do Gato/genética , Variações do Número de Cópias de DNA , Feminino , Testes Genéticos , Humanos , Cariotipagem , Trissomia/diagnóstico , Trissomia/genética
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(7): 779-784, 2020 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-32619264

RESUMO

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the detection of fetal copy number variations (CNVs) in addition to trisomies 21, 18, and 13. METHODS: A total of 37 306 pregnant women underwent the NIPT test. For those with fetal CNVs indicated by NIPT and accepted invasive prenatal diagnosis, amniotic fluid samples were obtained for chromosomal karyotyping analysis and chromosome microarray analysis (CMA). All cases were followed up. RESULTS: Among the 37 306 cases, 78 (0.209%) were predicted to have fetal CNVs. Among these, 52 pregnant women accepted invasive prenatal diagnosis, and 15 of them (28.85%) obtained a consistent result. Follow up of 26 women who refused invasive prenatal diagnosis have found 2 cases with spontaneous abortion, 2 with induced labor for fetal malformation indicated by ultrasonography, and 1 had multiple malformations and a consistent result by CMA, which yielded an abnormal rate of 19.23%. CONCLUSION: NIPT can signal fetal chromosomal abnormalities through detection of gain and/or loss of fetal DNA copies. Combined chromosomal karyotyping and CMA can increase the detection rate for common chromosomal aneuploidies and CNVs, thereby provide a basis for genetic counseling for the affected families.


Assuntos
Variações do Número de Cópias de DNA , Cariotipagem , Diagnóstico Pré-Natal , Trissomia , Aneuploidia , Feminino , Humanos , Gravidez , Trissomia/diagnóstico , Trissomia/genética
11.
Cytogenet Genome Res ; 160(4): 177-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369810

RESUMO

Nonmosaic trisomy involving 19p13.3p13.2 is a very uncommon abnormality. At present, only 12 cases with this genetic condition have been reported in the literature. However, the size of the trisomic fragment is heterogeneous and thus, the clinical spectrum is variable. Herein, we report the clinical and cytogenetic characterization of a 5-year-old boy with nonmosaic trisomy 19p13.3p13.2 (7.38 Mb), generated by a derivative Y chromosome resulting from a de novo unbalanced translocation t(Y;19)(q12;p13.2). We demonstrated the integrity of the euchromatic regions in the abnormal Y chromosome to confirm the pure trisomy 19p. Our patient shares some clinical features described in other reported patients with pure trisomy 19p, such as craniofacial anomalies, developmental delay, and heart defects. Different to previous reports, our case exhibits frontal pachygyria and polymicrogyria. These additional features contribute to further delineate the clinical spectrum of trisomy 19p13.3p13.2.


Assuntos
Cromossomos Humanos Par 19/genética , Cromossomos Humanos Y/genética , Lisencefalia/genética , Polimicrogiria/genética , Translocação Genética/genética , Trissomia/genética , Pré-Escolar , Humanos , Lisencefalia/patologia , Masculino , Mosaicismo , Pais , Polimicrogiria/patologia , Trissomia/patologia , Adulto Jovem
12.
Cytogenet Genome Res ; 160(3): 118-123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32248198

RESUMO

We present 2 cases of double mosaic aneuploidy harboring 2 or more different aneuploid cell lines, but no line with a normal chromosome constitution. One of these cases presented mosaicism of sex chromosome aneuploid cell lines (47,XXX/45,X) along with another line containing an autosomal trisomy (47,XX,+8), while the other case showed mosaicism of 2 different autosomal trisomy cell lines (47,XY,+5 and 47,XY,+8). To elucidate the mechanisms underlying these mosaicisms, we conducted molecular cytogenetic analyses. Genotyping data from the SNP microarray indicated that 2 sequential meiotic or early postzygotic segregation errors likely had occurred followed by natural selection. These cases suggest that frequent segregation errors and selection events in the meiotic and early postzygotic stages lead to this condition.


Assuntos
Linhagem da Célula/genética , Mosaicismo , Cromossomos Sexuais/genética , Trissomia/genética , Aneuploidia , Análise Citogenética , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Trissomia/patologia
13.
Acta Obstet Gynecol Scand ; 99(6): 765-774, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32306377

RESUMO

INTRODUCTION: Currently fetal nuchal translucency (NT) ≥3.5 mm is an indication for invasive testing often followed by chromosomal microarray. The aim of this study was to assess the risks for chromosomal aberrations in fetuses with an NT 3.0-3.4 mm, to determine whether invasive prenatal testing would be relevant in these cases and to assess the residual risks in fetuses with normal non-invasive prenatal test (NIPT) results. MATERIAL AND METHODS: A retrospective study and meta-analysis of literature cases with NT between 3.0 and 3.4 mm and 2 cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed: Rotterdam region (with a risk >1:200 and NT between 3.0 and 3.4 mm) tested in the period July 2012 to June 2019 and Central Denmark region (with a risk >1:300 and NT between 3.0 and 3.4 mm) tested between September 2015 and December 2018. RESULTS: A total of 522 fetuses were referred for invasive testing and chromosomal microarray. Meta-analysis indicated that in 1:7.4 (13.5% [95% CI 8.2%-21.5%]) fetuses a chromosomal aberration was diagnosed. Of these aberrant cases, 47/68 (69%) involved trisomy 21, 18, and 13 and would potentially be detected by all NIPT approaches. The residual risk for missing a (sub)microscopic chromosome aberration depends on the NIPT approach and is highest if NIPT was performed only for common trisomies-1:21 (4.8% [95% CI 3.2%-7.3%]). However, it may be substantially lowered if a genome-wide 10-Mb resolution NIPT test was offered (~1:464). CONCLUSIONS: Based on these data, we suggest that the NT cut-off for invasive testing could be 3.0 mm (instead of 3.5 mm) because of the high risk of 1:7.4 for a chromosomal aberration. If women were offered NIPT first, there would be a significant diagnostic delay because all abnormal NIPT results need to be confirmed by diagnostic testing. If the woman had already received a normal NIPT result, the residual risk of 1:21 to 1:464 for chromosome aberrations other than common trisomies, dependent on the NIPT approach, should be raised. If a pregnant woman declines invasive testing, but still wants a test with a broader coverage of clinically significant conditions then the genome-wide >10-Mb resolution NIPT test, which detects most aberrations, could be proposed.


Assuntos
Aberrações Cromossômicas , Análise em Microsséries , Teste Pré-Natal não Invasivo , Medição da Translucência Nucal , Estudos de Coortes , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Trissomia/diagnóstico , Trissomia/genética
14.
Acta Obstet Gynecol Scand ; 99(6): 775-782, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32346853

RESUMO

INTRODUCTION: Invasive prenatal testing with chromosomal microarray analysis may be a relevant option for all pregnant women, but there is only moderate-quality evidence for such an offer. We intended to study the prevalence of copy number variants (CNVs) in prenatal samples using a single SNP-array platform stratified by indication. MATERIAL AND METHODS: A cross-sectional study was performed based on a cohort. From January 2015 to December 2017, a total of 10 377 prenatal samples were received for prenatal single nucleotide polymorphism (SNP)-array in the laboratory of the Genetics Generation Advancement Corporation. Indications for chromosomal microarray analysis studies included the confirmation of an abnormal karyotype, ultrasound abnormalities, advanced maternal age and parental anxiety. CNVs and region of homozygosity identified by the SNP-array were analyzed. RESULTS: Of 10 377 cases, 689 had ultrasound abnormalities and 9688 were ascertained to have other indications. The overall prevalence of CNVs was 2.1% (n = 223/10 377, 95% confidence interval [CI] 1.9-2.4), but the prevalence was 4.4% (95% CI 3.0-6.1) for cases referred with abnormal ultrasound findings and 2.0% (95% CI 1.7-2.3) for other indications. Of the 223 CNVs detected, 42/10 377 were pathogenic (0.4%, 95% CI 0.3-0.6), 84 were susceptibility CNV (0.8%, 95% CI 0.6-1.0) and 97 were variants of uncertain significance (0.9%, 95% CI 0.8-1.1). Using an SNP-based platform allowed for the detection of paternal uniparental disomy of chromosome 14 in a fetus with ultrasound abnormality. CONCLUSIONS: With an indication of advanced maternal age but normal ultrasound scans, the prevalence of pathogenic CNVs was 0.4% and that of susceptibility CNV 0.7%. As CNVs are independent of maternal age, the prevalence is likely the same for younger women. Thus, this study provides further evidence that chromosomal microarray analysis should be available for all women who wish to receive diagnostic testing, as this risk is above the cut-off of 1:300 for Down syndrome, leading to the suggestion of invasive testing. A chromosomal microarray analysis based on SNP-array platform is preferable, as it can also detect uniparental disomy in addition to copy number variants.


Assuntos
Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Análise em Microsséries , Diagnóstico Pré-Natal , Adulto , Estudos Transversais , Feminino , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez , Prevalência , Trissomia/diagnóstico , Trissomia/genética
15.
Ann Biol Clin (Paris) ; 78(2): 187-190, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32319947

RESUMO

Acute myeloid leukemia (AML) with inv(16) is primarily associated with the eosinophilic LAM4 form belonging to the favorable prognosis group of AML. We report the case of an 18-year-old man with acute myeloid leukemia with unusual inversion of chromosome 16. Cytological, phenotypic and cytogenetic investigations showed a divergence from those in the literature. Indeed, the myelogram shows a medullary infiltration by elements blocked at the stage of myeloblates/promyelocytes, containing Auer rods grouped sometimes in fagots in blasts, promyelocytes and neutrophils. In view of this pathognomonic aspect, the diagnosis of AML type M3 is mentioned but quickly questioned by the results of immunophenotyping in favor of a maturing AML (M2). The karyotype and the FISH later objectify a recurrent anomaly "cytologically unexpected" inversion 16 (p13, q22) associated with trisomy 22.


Assuntos
Inversão Cromossômica , Cromossomos Humanos Par 16 , Leucemia Mieloide Aguda/diagnóstico , Adolescente , Cromossomos Humanos Par 22/genética , Citodiagnóstico , Análise Citogenética , Humanos , Imunofenotipagem , Cariotipagem , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/genética , Masculino , Trissomia/diagnóstico , Trissomia/genética
16.
Medicine (Baltimore) ; 99(14): e19730, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243411

RESUMO

RATIONALE: Co-occurrence of cytogenetic and molecular abnormalities is frequently seen in patients with acute myeloid leukemia (AML). The clinical outcome and genetic abnormalities of AML may vary; therefore, genetic investigation must be complex, using several techniques, to have an appropriate characterization of the AML genome and its clinical impact. The available molecular markers can predict prognosis only partially. Acute promyelocytic leukemia subtype M3 (AML M3) is a subtype of AML characterized by the presence of promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) genes fusion. Targeted treatment with all-trans-retinoic acid (ATRA) and ATRA combined with arsenic trioxide significantly improved the survival of AML M3 patients. Unknown prognostic factors could contribute to the early death of these patients. PATIENT CONCERNS: We present the case of a young female (20 years old) patient, who presented at the emergency department 5 months after giving birth to her first child, complaining of asthenia, fatigue, general musculoskeletal pain, and fever (38°C), symptoms having been present for the previous 6 days. The patient denied any chronic diseases in her medical and family history. DIAGNOSIS: Laboratory analysis revealed severe pancytopenia. Cytogenetic and molecular analyzes revealed chromosomal abnormalities (trisomy 8), PML-RARA gene fusion, and fms-like tyrosine kinase 3 (FLT3) gene mutation. The immunophenotypic analysis was also suggestive for AML M3 according to the FAB classification. INTERVENTIONS: Specific treatment was initiated for AML M3 and for secondary conditions. Molecular and cytogenetic analyzes were performed to have a more detailed characterization of the patient's genome. OUTCOME: Seventy-two hours after admission, she developed psychomotor agitation, confusion, coma, and convulsion. Subsequent deterioration and early death were caused by intracerebral hemorrhage with multiple localization and diffuse cerebral edema. LESSONS: The presence of FLT3 internal tandem duplication (ITD) mutation may explain the rapid and progressive degradation of this AML M3 case and it may be used as a prognostic marker even when co-occuring with other markers such as PML-RARA gene fusion and trisomy 8. We consider that FLT3 ITD mutation analysis in young patients with AML should be performed as soon as possible. New strategies for patients' education, AML (or cancers in general) prevention, and treatment are needed.


Assuntos
Fusão Gênica/genética , Leucemia Mieloide Aguda/genética , Proteína da Leucemia Promielocítica/genética , Receptor alfa de Ácido Retinoico/genética , Trissomia/genética , Tirosina Quinase 3 Semelhante a fms/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 8/genética , Evolução Fatal , Feminino , Humanos , Mutação , Sequências de Repetição em Tandem , Adulto Jovem
17.
Gene ; 741: 144533, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32145327

RESUMO

BACKGROUND: Syncytin-1 and syncytin-2 which are endogenous retroviral genes products play a great role in syncytialization during trophoblast differentiation in normal placental tissues. In aneuploidic placentas due to the low level of pregnancy-induced hormones an alteration was occurred in the syncytialization process, while in the presence of cytogenetically abnormal karyotype the effect of syncytin gene expression levels on syncytialization process and in occured to spontaneous abortions is not clear. To reveal this, we investigated in syncytin-1 and syncytin-2 genes expression levels of chromosomally abnormal and normal trophophoblastic tissues and we also discussed the effect of the syncytin gene expression levels to the occurense of the spontaneous abortion. MATERIAL AND METHODS: To each one of the trophoblastic cells; cultivation, harvesting, banding, and analysis were performed and the chromosomes were classified according to the presence of abnormality and normal XY constitution. To exclude the maternal decidual cell contamination, female karyotyped abortion materials were omitted in control group. The patient group consisted of thirty six placental tissues including trisomy 16 (n = 10), triploidy (n = 9), monosomy X (n = 9), trisomy 21 (n = 5) and trisomy 7 (n = 3). The control group was consisting twenty placental tissues with XY karyotypes. The some part of the dissected frozen trophoblastic cells were used for RNA isolation and were proceeded to the determination of the expression levels of syncytin-1 and syncytin-2 genes by single-step Real Time PCR. The cDNAs were obtained by probes used in the same PCR stages. The sequence analysis of the syncytin-1 and syncytin-2 genes were performed, and read by the usage of the FinchTV 1.4.0 program. RESULTS: Between the expression levels of syncytin-1 and syncytin-2 genes were statistically difference in the patients and controls. There was a difference (p < 0.0001) between trisomy 7 and other patient groups and controls, regarding to the expression of syncytin-1 gene. Numerous mutations in the syncytin-1 and syncytin-2 genes (on the expression sites) were detected, and the mutation rate was higher in the syncytin-1 gene compared to the syncytin-2 gene in the patient and in the control groups (p < 0.001). CONCLUSION: The results of the study indicate that the expression of the syncytin-2 genes could be altered in the presence of chromosomally abnormal trophoblastic tissues, and these could lead to the loss of pregnancy due to the insufficient syncytialization. In sum, the current research has value for the further studies covering the mechanisms of trophoblast cell fusion, and syncytiotrophoblast regeneration, and thus the pathophysiology of human placental development in the presence of genomic anomaly.


Assuntos
Cariótipo Anormal , Aborto Espontâneo/genética , Produtos do Gene env/economia , Proteínas da Gravidez/economia , Proteínas da Gravidez/genética , Feto Abortado/patologia , Aborto Induzido/métodos , Aborto Espontâneo/patologia , Adulto , Diferenciação Celular/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Cariótipo , Placenta/metabolismo , Gravidez , Trissomia/genética , Trissomia/patologia , Trofoblastos/patologia , Síndrome de Turner/genética , Síndrome de Turner/patologia , Adulto Jovem
18.
Zhonghua Fu Chan Ke Za Zhi ; 55(2): 106-111, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32146739

RESUMO

Objective: To evaluate the efficacy of cell free DNA (cf-DNA) screening in prenatal care by analyzing the follow-up information and pregnancy outcomes. Methods: All cf-DNA cases conducted in Women's Hospital of Nanjing Medical University from August 2011 to December 2017 were enrolled. The general information of the pregnancies, cf-DNA results, confirmatory testing results, and the follow-up results were collected. The pregnancy outcomes were analyzed in cases with low risk cf-DNA results as well as with high risk results for common trisomies, which were trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13). The sensitivity, specificity, positive predictive value and negative predictive value of cf-DNA screening were calculated. Results: (1) A total of 43 615 cf-DNA cases were involved, with 44 cases (0.10%, 44/43 615) test failure results, 314 cases (0.72%, 314/43 571) high risk results for common trisomies and 43 257 cases (99.27%, 43 257/43 571) low risk results. (2) Among 277 cases (88.21%, 277/314) high risk cases were successfully followed up, and 228 cases (82.31%, 228/277) underwent invasive confirmatory prenatal diagnosis. In the low risk results, 36 826 cases (85.13%, 36 826/43 257) were successfully followed up, and 572 (1.55%, 572/36 826) cases were found to have adverse pregnancy outcomes, among which 4 false negative cf-DNA results were confirmed. (3) In the 37 103 successfully followed up cf-DNA cases, the sensitivity for T21, T18, T13 were calculated as 97.96%, 96.67% and 100.00%, respectively; the specificity for T21, T18, T13 were calculated as 99.96%, 99.95% and 99.95%, respectively. The positive predictive value for T21, T18, T13 were calculated as 90.57%, 63.04% and 17.39%, respectively. The negative predictive value for T21, T18, T13 were calculated as 99.99%, 99.98% and 100.00%. Conclusions: Cf-DNA is effective in detecting common trisomies, with a high sensitivity and specificity. However, the follow-up information revealed several potential limitations in current clinical practice, such as a number of cases with high risk results rejected invasive confirmatory testing, as well as the genetic diagnostic results for most low risk cases with an adverse pregnancy outcome aren't obtained. Genetic counseling and the follow-up for all the cf-DNA cases should be emphasized in the future.


Assuntos
Ácidos Nucleicos Livres , Transtornos Cromossômicos/diagnóstico , Diagnóstico Pré-Natal/métodos , Trissomia/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 18/genética , Feminino , Seguimentos , Testes Genéticos/métodos , Humanos , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Sensibilidade e Especificidade , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18 , Ultrassonografia Pré-Natal
19.
Cytogenet Genome Res ; 160(3): 124-133, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32187602

RESUMO

Trisomy 14 is incompatible with live, but there are several patients reported with mosaic trisomy 14. We aimed to study the pattern of X inactivation and its effect on a translocated autosome and to find out an explanation of the involvement of chromosome 14 in 2 different structural chromosomal abnormalities. We report on a girl with frontal bossing, hypertelorism, low-set ears, micrognathia, cleft palate, congenital heart disease, and abnormal skin pigmentations. The patient displayed iris, choroidal, and retinal coloboma and agenesis of the corpus callosum and cerebellar vermis hypoplasia. Cytogenetic analysis revealed a karyotype 45,X,der(X)t(X;14)(q24;q11)[85]/46,XX,rob(14;14)(q10;q10),+14[35]. Array-CGH for blood and buccal mucosa showed high mosaic trisomy 14 and an Xq deletion. MLPA detected trisomy 14 in blood and buccal mucosa and also showed normal methylation of the imprinting center. FISH analysis confirmed the cell line with trisomy 14 (30%) and demonstrated the mosaic deletion of the Xq subtelomere in both tissues. There was 100% skewed X inactivation for the t(X;14). SNP analysis of the patient showed no region of loss of heterozygosity on chromosome 14. Also, genotype call analysis of the patient and her parents showed heterozygous alleles of chromosome 14 with no evidence of uniparental disomy. Our patient had a severe form of mosaic trisomy 14. We suggest that this cytogenetic unique finding that involved 2 cell lines with structural abnormalities of chromosome 14 occurred in an early postzygotic division. These 2 events may have happened separately or maybe there is a kind of trisomy or monosomy rescue due to dynamic cytogenetic interaction between different cell lines to compensate for gene dosage.


Assuntos
Anormalidades Múltiplas/genética , Trissomia/genética , Inativação do Cromossomo X/genética , Anormalidades Múltiplas/fisiopatologia , Pré-Escolar , Cromossomos Humanos Par 14/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Cariotipagem , Mosaicismo , Fenótipo , Translocação Genética/genética , Trissomia/fisiopatologia
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