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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.
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
3.
Pediatr Cardiol ; 41(7): 1319-1333, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32924070

RESUMO

There has been substantial controversy regarding treatment of congenital heart defects in infants with trisomies 13 and 18. Most reports have focused on surgical outcomes versus expectant treatment, and rarely there has been an effort to consolidate existing evidence into a more coherent way to help clinicians with decision-making and counseling families. An extensive review of the existing literature on cardiac surgery in patients with these trisomies was conducted from 2004 to 2020. The effects of preoperative and perioperative factors on in-hospital and long-term mortality were analyzed, as well as possible predictors for postoperative chronic care needs such as tracheostomy and gastrostomy. Patients with minimal or no preoperative pulmonary hypertension and mechanical ventilation undergoing corrective surgery at a weight greater than 2.5 kg suffer from lower postoperative mortality. Infants with lower-complexity cardiac defects are likely to benefit the most from surgery, although their expected mortality is higher than that of infants without trisomy. Omphalocele confers an increased mortality risk regardless of cardiac surgery. Gastrointestinal comorbidities increased the risk of gastrostomy tube placement, while those with prolonged mechanical ventilation and respiratory comorbidities are more likely to require tracheostomy. Cardiac surgery is feasible in children with trisomies 13 and 18 and can provide improved long-term results. However, this is a clinically complex population, and both physicians and caretakers should be aware of the long-term challenges these patients face following surgery when discussing treatment options.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Tomada de Decisão Clínica , Cardiopatias Congênitas/cirurgia , Síndrome da Trissomia do Cromossomo 13/cirurgia , Síndrome da Trissomía do Cromossomo 18/cirurgia , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , Guias de Prática Clínica como Assunto , Respiração Artificial , Fatores de Risco , Traqueostomia , Resultado do Tratamento , Trissomia , Síndrome da Trissomia do Cromossomo 13/mortalidade , Síndrome da Trissomía do Cromossomo 18/mortalidade
4.
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
5.
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
6.
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
7.
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
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): 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
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1183-1185, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924131

RESUMO

With an incidence of 1/800 - 1/600, Down syndrome (DS) is the most common chromosomal disorder in humans. Whilst most DS patients has trisomy 21, a small proportion may carry translocations or mosaicisms involving chromosome 21. The main characteristics of DS include mental retardation, peculiar facies, growth retardation, congenital heart disease, duodenal stenosis, Alzheimer's disease, leukemia, and immunodeficiency, which may be due to increased dosage of critical genes. Recent studies also showed that epigenetic changes may also occur in DS. For research on patients with DS or other trisomies have been restricted by ethical considerations, and commonly used mouse models cannot fully replicate the characteristic features of DS, pluripotent stem cells induced from fetal samples or biopsy tissues from DS patients may generate models with the same genetic content, which may provide idea materials for studying the pathogenesis of DS and customized cell and/or gene therapies.


Assuntos
Síndrome de Down , Células-Tronco Pluripotentes Induzidas , Animais , Cromossomos Humanos Par 21 , Síndrome de Down/genética , Humanos , Camundongos , Modelos Biológicos , Trissomia
12.
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
13.
Nat Commun ; 11(1): 3987, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778678

RESUMO

Aneuploidy, the presence of an abnormal number of chromosomes, is a major cause of early pregnancy loss in humans. Yet, the developmental consequences of specific aneuploidies remain unexplored. Here, we determine the extent of post-implantation development of human embryos bearing common aneuploidies using a recently established culture platform. We show that while trisomy 15 and trisomy 21 embryos develop similarly to euploid embryos, monosomy 21 embryos exhibit high rates of developmental arrest, and trisomy 16 embryos display a hypo-proliferation of the trophoblast, the tissue that forms the placenta. Using human trophoblast stem cells, we show that this phenotype can be mechanistically ascribed to increased levels of the cell adhesion protein E-CADHERIN, which lead to premature differentiation and cell cycle arrest. We identify three cases of mosaicism in embryos diagnosed as full aneuploid by pre-implantation genetic testing. Our results present the first detailed analysis of post-implantation development of aneuploid human embryos.


Assuntos
Aneuploidia , Implantação do Embrião/genética , Embrião de Mamíferos , Desenvolvimento Embrionário , Antígenos CD/genética , Caderinas/genética , Caderinas/metabolismo , Adesão Celular , Pontos de Checagem do Ciclo Celular , Linhagem da Célula , Segregação de Cromossomos , Cromossomos Humanos Par 16 , Cromossomos Humanos Par 21 , Feminino , Genes erbB-1/genética , Testes Genéticos , Humanos , Monossomia , Mosaicismo , Gravidez , Células-Tronco , Trissomia
14.
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
15.
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
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(6): 603-608, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32472533

RESUMO

OBJECTIVE: To explore the cause for the failure of non-invasive prenatal testing (NIPT) and feasibility of repeated testing. METHODS: Clinical data, test results and pregnancy outcomes of 40 311 pregnant women who received NIPT test from January 2011 to December 2018 were reviewed. RESULTS: Among all the pregnant women, 1116 cases failed in the first test, 9 cases (0.81%) had fetal free DNA concentration lower than 4%, 663 cases (59.41%) were retested after the establishment of Z value gray area, and the remainder 444 cases (39.78%) needed to be retested after the blood collection due to the fetal free DNA concentration lower than 4%. After retesting, 1069 cases (95.78%) obtained effective NIPT results. The results showed that 53 cases were at high risk (6 cases for trisomy 21, 6 cases for trisomy 18, 13 cases for trisomy 13, 16 cases for sex chromosomal abnormality, 12 cases for chromosomal copy number variation). Forty-eight cases were selected for invasive prenatal diagnosis, and 2 cases of 47, XXY and 2 CNV were confirmed. A total of 47 cases (0.12%) did not obtain results because the concentration of fetal free DNA was lower than 4%. Only 16 cases (34%) chose invasive prenatal diagnosis. CONCLUSION: Repeated detection of the gray area of Z value can reduce the false positive rate of NIPT and invasive prenatal diagnosis, and the feasibility of repeated detection is high. In the case of fetal free DNA concentration lower than 4%, the success rate of obtaining effective NIPT results by re-sampling and re-detection increases with the increase of gestational age, but may delay the diagnosis for fetal aneuploidies. Therefore, personalized estimation should be made according to gestational age and clinical indications. It is suggested that pregnant women should choose invasive prenatal diagnosis when they have failed in the retest.


Assuntos
Diagnóstico Pré-Natal , Aneuploidia , Transtornos Cromossômicos , Variações do Número de Cópias de DNA , Estudos de Viabilidade , Feminino , Humanos , Masculino , Gravidez , Trissomia
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(6): 609-612, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32472534

RESUMO

OBJECTIVE: To derive more sensitive and accurate Z-scores for noninvasive prenatal testing of fetal trisomies based on a combined DNA count- and size- algorithm. METHODS: One hundred eighty women at a high risk for fetal aneuploidies underwent amniocentesis. An effective cut-off value for DNA size ratio was explored. Conventional count-based Z-scores and size ratio-corrected Z scores were calculated. The reliability of each Z-score was assessed through comparison with the results of cytogenetic analysis. RESULTS: With the cut-off value set as 150 bp, the ratio of small DNA is positively correlated with the proportion of fetal DNA. The sensitivity and specificity of conventional count-based Z-scores were 75.00%, and 98.86%, respectively. This rate has increased to nearly 100% with a count-based 150 bp size correction. CONCLUSION: Compared with count-based methods alone, count-based Z-scores with 150 bp size correction may better predict fetal trisomies.


Assuntos
Diagnóstico Pré-Natal , Algoritmos , Aneuploidia , DNA , Feminino , Humanos , Gravidez , Reprodutibilidade dos Testes , Trissomia
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(6): 613-616, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32472535

RESUMO

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the diagnosis of fetal chromosomal aneuploidies among women with advanced gestational age. METHODS: 14 047 pregnant women have voluntarily accepted the NIPT test. The results of NIPT and amniocytic karyotyping analysis were compared, and the outcome of pregnancy was followed up. RESULTS: NIPT has identified 104 cases with a high risk for trisomies 21, 18 and 13, and 44 cases with a high risk for sex chromosome abnormalities. After genetic consultation, 87 of 104 cases have accepted amniocyte chromosomal karyotyping. 63 cases of fetal chromosome abnormality were confirmed, including 46 cases of 21 trisomy, 11 cases of 18 trisomy and 6 cases of 13 trisomy. The positive predictive value was 83.64% (46/55), 61.11% (11/18), and 42.86% (6/14), the specificity was 99.93%, 99.95%, 99.94%, and the sensitivity was 100%. Among the 44 cases, 34 received amniocytic chromosomal karyotyping analysis, 11 cases were confirmed, the positive predictive value was only 32.35%. No aneuploidy was found in the low-risk cases. The negative predictive value was 100%. CONCLUSION: As a prenatal screening method for women with advanced gestational age, NIPT has the highest positive predictive value for trisomy 21 and trisomy 18, but a lower positive predictive value for sex chromosome abnormalities. NIPT has a very low rate of missed diagnosis of trisomies 21, 18 and 13, which can significantly reduce the number of women undergoing invasive prenatal diagnosis.


Assuntos
Transtornos Cromossômicos , Diagnóstico Pré-Natal , Feminino , Testes Genéticos , Humanos , Gravidez , Trissomia , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(6): 621-626, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32472537

RESUMO

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of sex chromosome aneuploidies (SCAs), copy number variants (CNVs) and rare autosomal trisomies (RATs). METHODS: A total of 11 429 women with singleton pregnancy in Ningbo area were screened by NIPT. 106 women were subjected to invasive prenatal diagnosis due to high risk of chromosomal abnormalities other than 21, 18 and 13 aneuploidies. All cases were followed up for pregnancy outcome and postnatal status. RESULTS: Sixty-six women were signaled by NIPT for fetal SCAs, among whom 54 were willing to undergo prenatal diagnosis. Eighteen cases of fetal SCAs were verified as true positives and 4 were suspected positives, which yielded a positive predictive value (PPV) of 33.3%. Half of the women decided to continue their pregnancy. Forty women were signaled by NIPT for fetal CNVs, among which 32 underwent prenatal diagnosis. 19 cases of fetal CNVs were verified as true positives and 3 cases were suspected positives, which yielded a PPV of 46.8%. All women with pathological or possibly pathological CNVs decided to terminate their pregnancies. Thirty-one women were signaled for with fetal RATs. Two fetuses were confirmed to harbor mosaicism trisomies by prenatal diagnosis, and 1 case was suspected to be positive, which yielded a PPV of 9.7%. All of the three women have decided to terminate their pregnancy. CONCLUSION: In addition to aneuploidies of target chromosomes, NIPT also has important value for the detection of SCAs and CNVs. The results can help to further reduce birth defects. Nevertheless, in view of its low PPV, pregnant women with positive result still need appropriate genetic counseling and prenatal diagnosis to avoid unnecessary induced labor.


Assuntos
Transtornos Cromossômicos , Aneuploidia , Variações do Número de Cópias de DNA , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal , Aberrações dos Cromossomos Sexuais , Trissomia
20.
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
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