Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.533
Filtrar
2.
Fertil Steril ; 113(4): 853-864, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32228881

RESUMO

OBJECTIVE: To determine whether the incidence of chromosomal abnormalities in blastocysts is higher in patients with idiopathic recurrent pregnancy loss (iRPL) who underwent preimplantation genetic testing for aneuploidy (PGT-A) than in those who underwent preimplantation genetic testing for monogenic defects (PGT-M). DESIGN: Retrospective cohort study. SETTING: University-affiliated reproductive center. PATIENT(S): A total of 62 patients with iRPL underwent 101 PGT-A cycles (iRPL group), and 212 patients underwent 311 PGT-M cycles (control group). INTERVENTIONS(S): Blastocyst biopsy and comprehensive chromosome screening technologies, including single-nucleotide polymorphism microarrays and next-generation sequencing. MAIN OUTCOME MEASURE(S): Incidence of chromosomal abnormalities in blastocysts and clinical miscarriage (CM) rate. RESULT(S): Stratification analysis by maternal age showed an increased incidence of chromosomal abnormalities in the iRPL group aged ≤35 years (48.9% vs. 36.9%), whereas no significant increase was found in the iRPL group aged >35 years (66.9% vs. 61.4%). After transfer of euploid embryos, women aged ≤35 years with iRPL exhibited an increased CM rate compared with the control group (26.1% vs. 3.1%). CONCLUSION(S): Young patients with iRPL have a significantly higher rate of chromosomal abnormalities in blastocysts compared with patients with no or sporadic CM. Although euploid embryos were transferred after PGT-A, young patients with iRPL had a higher CM rate, which may indicate that chromosomal abnormalities might not be the only causal factor for iRPL. Therefore, the role of PGT-A in iRPL still needs to be clarified.


Assuntos
Aborto Habitual/genética , Aneuploidia , Blastocisto/fisiologia , Aberrações Cromossômicas/embriologia , Diagnóstico Pré-Implantação/métodos , Aborto Habitual/diagnóstico , Adulto , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Estudos de Coortes , Feminino , Testes Genéticos/métodos , Humanos , Gravidez , Estudos Retrospectivos
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 389-391, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219819

RESUMO

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the analysis of 824 samples from miscarriage or stillbirth. METHODS: Copy number variations (CNVs) in the abortic chorionic villi or stillbirth tissues were detected by CMA. RESULTS: All specimens were successfully analyzed, among which 381 (46.2%) were diagnosed with chromosomal abnormalities, which included 312 (81.9%) numerical abnormalities, 66 (17.3%) structural abnormalities and 3 (0.8%) uniparental disomies. Among numerical chromosomal abnormalities, aneuploidies was most common (92.0%), with trisomy 16 and 45,X accounting for 41 (13.1%) and 63 (20.2%) of the cases, respectively. Among the 66 structural chromosomal aberrations, there were 26 (39.4%) CNVs duplications, 20 (30.3%) CNVs deletions, and 20 (30.3%) CNVs duplication and deletions. 33 CNVs were predicted as have a high chance to lead to a disease. CONCLUSION: CMA is a reliable, robust, and high-resolution method for the analysis of miscarriage or stillbirth samples. Numerical aberrations, in particular chromosomal aneuploides, are the main cause for spontaneous abortions and stillbirths.


Assuntos
Aborto Espontâneo/genética , Aberrações Cromossômicas , Transtornos Cromossômicos , Análise em Microsséries , Natimorto/genética , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Variações do Número de Cópias de DNA , Feminino , Humanos , Gravidez
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 392-396, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219820

RESUMO

OBJECTIVE: To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) for prenatal diagnosis. METHODS: G-banding karyotyping and CMA were simultaneously performed on 546 women who were subjected to amniocentesis during middle pregnancy. RESULTS: In total 82 cases were detected with chromosomal abnormalities. The two methods were consistent in 43 cases, which included 14 trisomy 21, 6 trisomy 18, 1 trisomy 13, 14 sex chromosomal aneuploidies, 4 chromosomal deletions, 3 chromosomal duplications and 1 sex chromosomal mosaicism. Fifteen fetuses with chromosomal abnormalities detected by CMA were missed by karyotyping analysis, which included 9 microdeletions and 6 microduplications. Sixteen fetuses with chromosomal abnormalities detected by karyotyping analysis were missed by CMA, which included 15 chromosomal translocations and 1 sex chromosomal mosaicism. In 7 cases, the results of karyotyping analysis and CMA were inconsistent. One supernumerary marker chromosome detected by karyotyping analysis was verified by CMA as 9p13.1p21.1 duplication. CONCLUSION: Combined chromosomal karyotyping and CMA can significantly improve the detection rate for chromosomal abnormalities, which has a great value for prenatal diagnosis.


Assuntos
Transtornos Cromossômicos , Cariotipagem , Análise em Microsséries , Diagnóstico Pré-Natal , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Feminino , Humanos , Gravidez
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 405-409, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219823

RESUMO

OBJECTIVE: To carry out genetic testing for 3 fetuses with abnormal prenatal screening. METHODS: Fetal ultrasound, karyotype analysis, single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization were performed. RESULTS: Abnormalities of chromosome 22 were found with all 3 fetuses. Fetus 1 harbored a 7.1 Mb deletion in 22q13.2q13.33 region, which involved 54 OMIM genes including SHANK3 and FBLN1. Fetus 2 had a mosaicism karyotype, with 12% of cells harboring a 6.6 Mb deletion in 22q13.31q13.33, covering 48 OMIM genes such as SHANK3 and PPARA, and 5% of cells harboring a 26.1 Mb duplication in 22q11.1q13.2 involving 285 OMIM genes. Fetus 3 carried a tandem duplication of 1.7 Mb in 22q11.1q11.21, which involved 10 OMIM genes including CECR1, CECR2 and ATP6V1E1. No abnormality was found in the three couples by chromosomal karyotyping and SNP array analysis. CONCLUSION: The severity of diseases caused by chromosome 22 abnormalities not only depends on the range of the deletion or duplication, but is also closely related to chromosome structure, gene dose and genetic environment. Combined ultrasonography and various genetic testing techniques in prenatal diagnosis can greatly increase the detection rate of genetic diseases with substantial phenotypic variation.


Assuntos
Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 22/genética , Testes Genéticos , Cariotipagem , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Aberrações Cromossômicas , Deleção Cromossômica , Transtornos Cromossômicos/genética , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Gravidez , Fatores de Transcrição
7.
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
9.
Hum Genet ; 139(4): 531-543, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32030560

RESUMO

We present a comprehensive clinically oriented workflow for large-insert genome sequencing (liGS)-based nucleotide level resolution and interpretation of de novo (dn) apparently balanced chromosomal abnormalities (BCA) in prenatal diagnosis (PND). Retrospective or concomitant with conventional PND and liGS, molecular and newly developed clinically inspired bioinformatic tools (TAD-GConTool and CNV-ConTool) are applied to analyze and assess the functional and phenotypic outcome of dn structural variants (dnSVs). Retrospective analysis of four phenotype-associated dnSVs identified during conventional PND precisely reveal the genomic elements disrupted by the translocation breakpoints. Identification of autosomal dominant disease due to the disruption of ANKS1B and WDR26 by t(12;17)(q23.1;q21.33)dn and t(1;3)(q24.11;p25.3)dn breakpoints, respectively, substantiated the proposed workflow. We then applied this workflow to two ongoing prenatal cases with apparently balanced dnBCAs: 46,XX,t(16;17)(q24;q21.3)dn referred for increased risk on combined first trimester screening and 46,XY,t(2;19)(p13;q13.1)dn referred due to a previous trisomy 21 pregnancy. Translocation breakpoints in the t(16;17) involve ANKRD11 and WNT3 and disruption of ANKRD11 resulted in KBG syndrome confirmed in postnatal follow-up. Breakpoints in the t(2;19) are within ATP6V1B1 and the 3' UTR of CEP89, and are not interpreted to cause disease. Genotype-phenotype correlation confirms the causative role of WDR26 in the Skraban-Deardorff and 1q41q42 microdeletion phenocopy syndromes, and that disruption of ANKS1B causes ANKS1B haploinsufficiency syndrome. In sum, we show that an liGS-based approach can be realized in PND care providing additional information concerning clinical outcomes of dnBCAs in patients with such rearrangements.


Assuntos
Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Transtornos Cromossômicos , Cromossomos Humanos/genética , Facies , Genes Dominantes , Deficiência Intelectual , Diagnóstico Pré-Natal , Anormalidades Dentárias , Translocação Genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Adolescente , Adulto , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/genética , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Masculino , Gravidez , Anormalidades Dentárias/diagnóstico , Anormalidades Dentárias/genética , Fluxo de Trabalho
10.
Z Geburtshilfe Neonatol ; 224(3): 153-159, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31853915

RESUMO

Within 4 years (2014-2017), we genetically diagnosed 2 newborns with Kagami-Ogata syndrome (OMIM #608149). As fetuses they exhibited prenatal polyhydramnios and in 1 case hepatomegaly. After birth, the newborns suffered from respiratory distress. Typical phenotypic features, such as muscular hypotonia, a protruding philtrum, full cheeks and a depressed nasal bridge, were present. Chest X-rays revealed coat-hanger ribs and a bell-shaped thorax, suggestive of the entity. Kagami-Ogata syndrome is caused by an aberrant gene expression of chromosome 14 and was first described in 1991. Possible causes are paternal uniparental disomy of chromosome 14, epimutations and microdeletions. Approximately 70 cases have been reported in the literature, with 34 comprising the original cohort of M. Kagami and T. Ogata. The incidence of the disease is unknown. Patients often manifest a developmental delay and an intellectual disability, although in the meantime cases with milder clinical courses have been described. In the cohort of Kagami and Ogata 3 patients developed hepatoblastoma, which is a common feature in another imprinting disorder, namely the Beckwith-Wiedemann syndrome. Therefore, hepatoblastoma should be considered in follow-up examinations.


Assuntos
Transtornos Cromossômicos/genética , Cromossomos Humanos Par 14/genética , Deficiência Intelectual/genética , Costelas/anormalidades , Tórax/anormalidades , Dissomia Uniparental/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Transtornos Cromossômicos/diagnóstico , Feminino , Impressão Genômica , Humanos , Recém-Nascido , Poli-Hidrâmnios , Gravidez , Costelas/diagnóstico por imagem , Tórax/diagnóstico por imagem
11.
Am J Obstet Gynecol ; 221(6): B10-B12, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31787157

Assuntos
Pé Torto Equinovaro/diagnóstico por imagem , Ultrassonografia Pré-Natal , Amniocentese , Síndrome de Bandas Amnióticas/complicações , Síndrome de Bandas Amnióticas/diagnóstico , Artrogripose/complicações , Artrogripose/diagnóstico , Doenças do Desenvolvimento Ósseo/complicações , Doenças do Desenvolvimento Ósseo/diagnóstico , Apresentação Pélvica/diagnóstico , Amostra da Vilosidade Coriônica , Transtornos Cromossômicos/complicações , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Transtornos da Motilidade Ciliar/complicações , Transtornos da Motilidade Ciliar/diagnóstico , Transtornos da Motilidade Ciliar/genética , Pé Torto Equinovaro/complicações , Pé Torto Equinovaro/diagnóstico , Pé Torto Equinovaro/etiologia , Pé Torto Equinovaro/genética , Diagnóstico Diferencial , Encefalocele/complicações , Encefalocele/diagnóstico , Encefalocele/genética , Feminino , Testes Genéticos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Humanos , Análise em Microsséries , Oligo-Hidrâmnio/diagnóstico , Síndrome de Pierre Robin/complicações , Síndrome de Pierre Robin/diagnóstico , Síndrome de Pierre Robin/genética , Doenças Renais Policísticas/complicações , Doenças Renais Policísticas/diagnóstico , Doenças Renais Policísticas/genética , Gravidez , Segundo Trimestre da Gravidez , Retinite Pigmentosa/complicações , Retinite Pigmentosa/diagnóstico , Retinite Pigmentosa/genética
12.
Am J Hum Genet ; 105(6): 1262-1273, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31785788

RESUMO

It has long been appreciated that genetic analysis of fetal or trophoblast cells in maternal blood could revolutionize prenatal diagnosis. We implemented a protocol for single circulating trophoblast (SCT) testing using positive selection by magnetic-activated cell sorting and single-cell low-coverage whole-genome sequencing to detect fetal aneuploidies and copy-number variants (CNVs) at ∼1 Mb resolution. In 95 validation cases, we identified on average 0.20 putative trophoblasts/mL, of which 55% were of high quality and scorable for both aneuploidy and CNVs. We emphasize the importance of analyzing individual cells because some cells are apoptotic, in S-phase, or otherwise of poor quality. When two or more high-quality trophoblast cells were available for singleton pregnancies, there was complete concordance between all trophoblasts unless there was evidence of confined placental mosaicism. SCT results were highly concordant with available clinical data from chorionic villus sampling (CVS) or amniocentesis procedures. Although determining the exact sensitivity and specificity will require more data, this study further supports the potential for SCT testing to become a diagnostic prenatal test.


Assuntos
Transtornos Cromossômicos/diagnóstico , Marcadores Genéticos , Teste Pré-Natal não Invasivo/métodos , Placenta/metabolismo , Trofoblastos/citologia , Trofoblastos/metabolismo , Adulto , Transtornos Cromossômicos/genética , Variações do Número de Cópias de DNA , Feminino , Humanos , Masculino , Placenta/citologia , Gravidez , Análise de Célula Única , Adulto Jovem
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1094-1096, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703133

RESUMO

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of fetal chromosomal aneuploidies. METHODS: For 9470 pregnant women with a moderate-to-high risk by conventional serological screening or advanced maternal age, peripheral venous blood samples were collected and, following extraction of free fetal DNA, subjected to large-scale parallel sequencing on a Illumina Hiseq2000 platform. Those with a high risk by NIPT were validated by invasive prenatal diagnosis. RESULTS: Out of the 9470 samples, 194 cases (2.0%) were positive by NIPT testing. These included 50 trisomy 21, 11 trisomy 18, 17 trisomy 13, 44 other autosomal aneuploidies, 55 sex chromosomal aneuploidies, and 17 chromosomal copy number variations. As validated by amniotic fluid or umbilical blood chromosomal karyotyping analysis, NIPT has a false positive rate of 2.0%, 18.2%, 41.2%, 97.7%, 81.8%, 94.1%, respectively. The test has a sensitivity of 100% and a specificity of 98.79%. CONCLUSION: For common chromosomal aneuploidies such as trisomy 21 and trisomy 18, NIPT has a good sensitivity and specificity, therefore has good value for clinical application.


Assuntos
Aneuploidia , Transtornos Cromossômicos/diagnóstico , Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Feminino , Humanos , Gravidez , Sensibilidade e Especificidade , Trissomia , Síndrome da Trissomía do Cromossomo 18
14.
Int J Mol Sci ; 20(21)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690017

RESUMO

In the prenatal period, the copy number aberrations of chromosomes 13, 18, 21, X and Y account for over 80% of the clinically significant chromosome abnormalities. Classical cytogenetic analysis is the gold standard in invasive prenatal diagnostics but the long test waiting time affects its clinical utility. Several molecular rapid tests have been developed and employed in clinical practice, however all have substantial drawbacks. The aim of the study was to design and evaluate an optimized tool for rapid molecular detection of fetal aneuploidies. We established a novel single-day method using a chip-based platform, the QuantStudio 3D Digital PCR system. In order to assess the clinical usefulness of our screening test, we analyzed 133 prenatal samples. The difference in distributions of euploid and aneuploid samples identified the ploidy of each of the target chromosomes with high precision. The distribution of the chromosome ratio for euploid and aneuploid samples showed a statistically significant result (p = 0.003 for trisomy 13, p = 0.001 for trisomies 18 and 21, Mann-Whitney U test). Our results suggest that this novel chip-based approach provides a tool for rapid, technically simple, cost-effective screening for common fetal aneuploidies.


Assuntos
Aneuploidia , Transtornos Cromossômicos/diagnóstico , Testes Genéticos/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Transtornos Cromossômicos/genética , Custos e Análise de Custo , Feminino , Testes Genéticos/economia , Testes Genéticos/normas , Humanos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/economia , Análise de Sequência com Séries de Oligonucleotídeos/normas , Reação em Cadeia da Polimerase/economia , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/normas , Gravidez , Diagnóstico Pré-Natal/economia , Diagnóstico Pré-Natal/normas , Sensibilidade e Especificidade
15.
J Assist Reprod Genet ; 36(12): 2525-2531, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31720905

RESUMO

PURPOSE: To establish a single-nucleotide polymorphism-based analysis (SBA) method to identify triploidy in the miscarriage tissue by using low-coverage whole-genome sequencing (LC-WGS). METHODS: The method was established by fitting a quadratic curve model by counting the distribution of three heterozygous mutation content intervals. The triploid test result was mainly determined by the opening direction and the axis of symmetry of the quadratic curve, and Z test between the same batch samples was also used for auxiliary judgment. RESULTS: Two hundred thirteen diploid samples and 8 triploid samples were used for establishment of the analytical method and 203 unknown samples were used for blind testing. In the blind testing, we found 2 cases positive for triploidy. After chromosome microarray analysis (CMA) and mass spectrometry verification, we found that both samples were true positives. We randomly selected 5 samples from the negative samples for mass spectrometry verification, and the results showed that these samples were all true negatives. CONCLUSIONS: Our method achieved accurate detection of triploidy in the miscarriage tissue and has the potential to detect more chromosomal abnormality types such as uniparental disomy (UPD) using a single LC-WGS approach.


Assuntos
Aborto Espontâneo/genética , Transtornos Cromossômicos/genética , Triploidia , Sequenciamento Completo do Genoma , Aborto Espontâneo/diagnóstico , Aborto Espontâneo/patologia , Adulto , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/patologia , Feminino , Humanos , Análise em Microsséries , Mutação , Polimorfismo de Nucleotídeo Único/genética , Gravidez
16.
BMJ Case Rep ; 12(11)2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31678916

RESUMO

A young man with neuropsychiatric problems has a small 22q13.33 duplication. We suggest this causes his condition. His disorder may represent a 22q13.33 behavioural phenotype. In childhood, he was diagnosed with mild intellectual disability. He was later diagnosed with Tourette syndrome, atypical autism spectrum disorder and bipolar disorder. Lithium seems effective in treating his affective symptoms. He has mild dysmorphic features, full lips and protruding ears. An array comparative genomic hybridisation showed a 300 kb duplication. The duplication harbours several genes, notably SH3 and multiple ankyrin repeat domain 3 (SHANK 3). The small size helps focus on a critical region for a 22q13.33 duplication syndrome. Mutations, deletions and duplications should be kept in mind as causes of neuropsychiatric disorders, especially in a patient with dysmorphic traits.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno Bipolar/diagnóstico , Transtornos Cromossômicos/diagnóstico , Deficiência Intelectual/diagnóstico , Síndrome de Tourette/diagnóstico , Antimaníacos/uso terapêutico , Transtorno do Espectro Autista/complicações , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Deleção Cromossômica , Transtornos Cromossômicos/complicações , Cromossomos Humanos Par 22 , Humanos , Deficiência Intelectual/complicações , Compostos de Lítio/uso terapêutico , Masculino , Proteínas do Tecido Nervoso/genética , Síndrome de Tourette/complicações , Síndrome de Tourette/tratamento farmacológico , Adulto Jovem
17.
Taiwan J Obstet Gynecol ; 58(6): 864-868, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759544

RESUMO

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 3. CASE REPORT: A 36-year-old woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+mar[6]/46,XX[18]. The mother's karyotype was 47,XX,+mar[4]/46,XX[46]. The father's karyotype was 46.XY. Array comparative genomic hybridization (aCGH) analysis of uncultured amniocytes revealed a result of arr 3q11.1q12.1 (93,575,285-98,956,687) × 2-3 [GRCh37 (hg19)]. Prenatal ultrasound findings were unremarkable. The parents elected to continue the pregnancy, and a 2470-g female baby was delivered at 37 weeks of gestation without phenotypic abnormalities. The cord blood had a karyotype of 47,XX,+mar[8]/46,XX[32]. aCGH analysis of cord blood revealed a result of arr 3q11.1q11.2 (93,649,973-97,137,764) × 2.4 [GRCh37 (hg19)] with a log2 ratio of 0.25 and a 30-40% mosaicism for 3.488-Mb dosage increase in 3q11.1-q11.2 encompassing four [Online Mendelian Inheritance in Man (OMIM)] genes of PROS1, ARL13B, NSUN3 and EPHA6. Metaphase fluorescence in situ hybridization (FISH) analysis confirmed 30% (6/20 cells) mosaicism for the sSMC(3) in the blood lymphocytes. CONCLUSION: aCGH and FISH analyses are useful for perinatal investigation of a prenatally detected sSMC.


Assuntos
Amniocentese/métodos , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 3/genética , Doenças Fetais/diagnóstico , Mosaicismo , Diagnóstico Pré-Natal/métodos , Adulto , Transtornos Cromossômicos/genética , Hibridização Genômica Comparativa , Feminino , Doenças Fetais/genética , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Gravidez
18.
Taiwan J Obstet Gynecol ; 58(6): 869-871, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759545

RESUMO

OBJECTIVE: We present a familial 21q22.3 microduplication in a fetus associated with prenatally detected congenital heart defects (CHD). CASE REPORT: A 38-year-old woman underwent amniocentesis at 22 weeks of gestation because of sonographic findings of double outlet of right ventricle, ventricular septal defect and transposition of great artery in the fetus. Her husband was 42 years old, and there was no CHD and congenital malformation in the family. Cytogenetic analysis revealed a karyotype of 46,XY in the fetus. Simultaneous array comparative genomic hybridization (aCGH) analysis using uncultured amniocytes revealed a 0.56-Mb microduplication of 21q22.3 or arr 21q22.3 (47,482,210-48,043,704)×3.0 [GRCh37 (hg19)] encompassing nine Online Mendelian Inheritance in Man (OMIM) genes of FTCD, SPATC1L, LSS, MCM3AP, YBEY, PCNT, DIP2A, S100B and PRMT2. aCGH analysis of the parental bloods revealed that the phenotypically normal father carried the same microduplication. The parents decided to continue the pregnancy, and a 3168-g male baby was delivered at term without Down syndrome phenotype except CHD. Mutational analysis of the CRELD1 gene on the DNA extracted from the cord blood showed no mutation in CRELD1. Postnatal molecular cytogenetic analysis of the cord blood confirmed the prenatal diagnosis. The infant underwent a successful heart surgery to correct the CHD and was doing well without psychomotor or developmental delay at six months of age. CONCLUSION: Prenatal diagnosis of 21q22.3 microduplication associated with CHD should include a differential diagnosis of Down syndrome.


Assuntos
Amniocentese/métodos , Transtornos Cromossômicos/diagnóstico , Duplicação Cromossômica/genética , Cromossomos Humanos Par 21/genética , Doenças Fetais/diagnóstico , Cardiopatias Congênitas/diagnóstico , Ultrassonografia Pré-Natal/métodos , Adulto , Transtornos Cromossômicos/genética , Feminino , Doenças Fetais/genética , Cardiopatias Congênitas/genética , Humanos , Cariótipo , Cariotipagem , Gravidez
19.
BMC Pregnancy Childbirth ; 19(1): 385, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660889

RESUMO

BACKGROUND: Genomics-based noninvasive prenatal tests (NIPT) allow screening for chromosomal anomalies such as Down syndrome (trisomy 21). The technique uses cell-free fetal DNA (cffDNA) that circulates in the maternal blood and is detectable from 5 weeks of gestation onwards. Parents who choose to undergo this relatively new test (introduced in 2011) might be aware of its positive features (i.e. clinical safety and ease of use); however, they might be less aware of the required decisions and accompanying internal conflicts following a potential positive test result. To show the evidence on psychological and social consequences of the use of NIPT, we conducted a scoping review. METHODS: We systematically searched four electronic databases (MEDLINE (Ovid), Cochrane Library (Wiley), CINAHL (EBSCO) and PsychINFO (EBSCO)) for studies that investigated the psychological or social consequences of the use of NIPT by pregnant women or expecting parents. The search was limited to studies published between 2011 and August 8, 2018. We identified 2488 studies and, after removal of duplicates, screened 2007 titles and abstracts, and then assessed 99 articles in full text (both screenings were done independently in duplicate). We included 7 studies in our analysis. RESULTS: Five studies assessed anxiety, psychological distress and/or decisional regret among women with validated psychological tests like the Spielberger State Trait-Anxiety Inventory (STAI), the Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R), the Kessler Psychological Distress Scale (K6) or the Decisional Regret Scale (DRS). Two studies assessed women's experiences with and feelings after NIPT in interviews or focus groups. The included studies were heterogeneous in location, study setting, inclusion criteria, outcome assessment, and other characteristics. CONCLUSIONS: Only few studies on psychological consequences of NIPT have been identified. The studies assessed only short-term psychological consequences of NIPT at baseline and/or after receiving the results or after giving birth. Studies show that short term anxiety decreased when women received negative NIPT results and that decisional regret was generally low. We could not identify studies on long term consequences of NIPT, as well as studies on women's partners' short and long term outcomes, nor on social consequences of NIPT.


Assuntos
Testes Genéticos/métodos , Diagnóstico Pré-Natal , Transtornos Cromossômicos/diagnóstico , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/psicologia , Psicologia
20.
Taiwan J Obstet Gynecol ; 58(5): 662-666, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542089

RESUMO

OBJECTIVE: Prenatal diagnosis of de novo segmental amplification or deletion by microarray-based comparative genomic hybridization (array CGH) is uncommon. The study aimed to know about the incidence, abnormal ultrasound findings, and pregnancy outcomes of prenatally diagnosed de novo segmental amplification or deletion by array CGH. MATERIALS AND METHODS: Between January 2014 and December 2017, we analyzed pregnant women who received prenatal array CGH (SurePrint G3 Human CGH Microarray Kit, 8 × 60K) at Chang Gung Memorial Hospital, Taiwan. Clinical data on maternal age, reason for fetal karyotyping, sonographic findings, gestational age at delivery, newborn birth weight, and associated anomalies, if any, were obtained by chart review. RESULTS: A total of 836 specimens (814 amniotic fluid samples, 4 cord blood samples, 18 chorionic villi samples) were analyzed by array CGH during the study period. Of the 56 cases with abnormal array CGH results, 40 had segmental amplification or deletion, 12 had trisomy, three had monosomy, and one had sex chromosome aneuploidy. Of these 40 cases with segmental amplification or deletion, 30 were inherited and 10 were de novo occurrences. The incidence of de novo segmental amplification or deletion was 1.2% (10/836). Abnormal prenatal ultrasound findings occurred in 40% (4/10) of de novo segmental amplification or deletion cases. Among these 10 pregnancies, nine were voluntarily terminated between 22 and 26 weeks of gestation and one was delivered at term. CONCLUSIONS: Prenatal diagnosis of de novo segmental amplification or deletion by array CGH raises important genetic counseling issues. In our series, the incidence of de novo segmental amplification or deletion in prenatal samples was 1.2%. Abnormal prenatal sonographic findings occurred in 40% of these de novo segmental amplification or deletion cases. Of these de novo segmental amplification or deletion pregnancies, 90% were voluntarily terminated.


Assuntos
Transtornos Cromossômicos/diagnóstico , Hibridização Genômica Comparativa/métodos , Amplificação de Genes/genética , Análise em Microsséries/métodos , Diagnóstico Pré-Natal/métodos , Deleção de Sequência/genética , Adulto , Peso ao Nascer , Aberrações Cromossômicas/embriologia , Transtornos Cromossômicos/embriologia , Transtornos Cromossômicos/genética , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Cariotipagem , Idade Materna , Técnicas de Amplificação de Ácido Nucleico , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Taiwan , Ultrassonografia Pré-Natal
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA