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1.
Cytogenet Genome Res ; 158(4): 199-204, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31315112

RESUMO

Here, we report a molecular characterization of a small supernumerary marker chromosome (sSMC) derived from the most proximal region of 13q present in a fetus with coarctation of the aorta at ultrasound examination during prenatal diagnosis. Cultured umbilical cord blood cells showed a de novo extra ring-shaped sSMC in 76% of the cells using a standard banding technique. SNP array revealed a tetrasomy of about 28.4 Mb in the long arm of chromosome 13 from band 13q11 to 13q14.11 in the fetus's cells. Metaphase/interphase FISH using specific probes located at 13q11, 13q12.11, and 13q14.11, respectively, demonstrated that the supernumerary ring chromosome was derived from an inverted duplication of the region 13q11q14.11 with a conventional centromere. To the best of our knowledge, this is the first time that an inverted duplication of the most proximal region 13q11q14.11 in a ring chromosome is characterized. The findings we presented here deepen our understanding of the clinical consequences of tetrasomy in this region and may be of help for further studies of critical regions in chromosome 13.


Assuntos
Coartação Aórtica/genética , Duplicação Cromossômica/genética , Cromossomos Humanos Par 13/genética , Doenças Fetais/genética , Diagnóstico Pré-Natal , Cromossomos em Anel , Tetrassomia/genética , Adulto , Centrômero/genética , Bandeamento Cromossômico , Feminino , Doenças Fetais/diagnóstico , Feto/metabolismo , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Polimorfismo de Nucleotídeo Único/genética , Gravidez
2.
Z Geburtshilfe Neonatol ; 223(3): 179-183, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31200400

RESUMO

Noninvasive prenatal testing (NIPT) is a screening test for fetal chromosome disorders. Recent studies show an incidental detection of maternal malignancies in NIPT diagnostics, where the simultaneous presence of multiple aneuploidies is described as an NIPT "anomaly". In this case, the diagnosis of a maternal tumor disease was made due to a repeat NIPT failure (no call).


Assuntos
Ácidos Nucleicos Livres , Transtornos Cromossômicos , Doenças Fetais , Neoplasias , Adulto , Aneuploidia , Transtornos Cromossômicos/diagnóstico , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Testes Genéticos , Humanos , Achados Incidentais , Programas de Rastreamento , Neoplasias/diagnóstico , Neoplasias/genética , Gravidez , Diagnóstico Pré-Natal
3.
J Coll Physicians Surg Pak ; 29(5): 483-485, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31036126

RESUMO

The aim of this study was to explore the feasibility of non-invasive prenatal genetic diagnosis of ß-thalassemia with small fragments of cell-free fetal DNA (cffDNA) in peripheral blood of pregnant women. It was an observational study carried out at Department of Obstetrics, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China, from January 2016 to March 2018. A total of 40 pregnant women, who were likely to give birth to babies with severe ß-thalassemia, were selected, and ß-globin genotype of the fetus was non-invasively detected by cffDNA in peripheral blood of their mothers. Small fragments of cffDNA from all specimens were successfully amplified. Compared with the results of traumatic prenatal diagnosis, 37 cases (92.50%) were diagnosed and 3 cases (7.50%) were misdiagnosed. The cffDNA in maternal plasma can be used for non-invasive prenatal genetic diagnosis of ß-thalassemia, and is worthy of promotion.


Assuntos
Ácidos Nucleicos Livres/sangue , DNA/sangue , DNA/genética , Amplificação de Genes/genética , Gravidez/sangue , Diagnóstico Pré-Natal/métodos , Globinas beta/genética , Talassemia beta/diagnóstico , Adulto , Ácidos Nucleicos Livres/genética , DNA/isolamento & purificação , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Feto/irrigação sanguínea , Testes Genéticos , Humanos , Gestantes , Talassemia beta/genética
4.
J Genet ; 982019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945666

RESUMO

The aim of the present study was to evaluate the diagnostic yield of prenatal cytogenetic microarray (CMA) in structurally normal and abnormal foetuses and record the acceptance rate of CMA for prenatal diagnosis over a course of five year. In 128 structurally normal and abnormal foetuses, CMA was performed along with foetal karyotype, after exclusion of aneuploidy by quantitative fluorescence polymerase chain reaction. The microarray was able to detect the pathogenic variants in 5.5% cases; the diagnostic yield in structurally abnormal foetuses was 8.8% and 4.7% in foetuses with a high aneuploidy risk. Balanced and unbalanced translocations, and low level mosaicism were detected. Reanalysis of variants of uncertain significance identified pathogenic variant. The study shows higher diagnostic yield in structurally abnormal cases, the importance of foetal karyotype and reanalysis in microarray. The acceptance rate of prenatal CMA increased five-fold over a period of five year.


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos/genética , Análise Citogenética/métodos , Doenças Fetais/genética , Testes Genéticos/normas , Análise em Microsséries/métodos , Diagnóstico Pré-Natal/métodos , Cariótipo Anormal , Adulto , Transtornos Cromossômicos/diagnóstico , Feminino , Doenças Fetais/diagnóstico , Humanos , Gravidez , Prognóstico
5.
BJOG ; 126(10): e173-e185, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30968555

RESUMO

WHAT IS IT?: Fetal neonatal alloimmune thrombocytopenia (FNAIT), also known as neonatal alloimmune thrombocytopenia (NAIT) or fetomaternal alloimmune thrombocytopenia (FMAIT), is a rare condition which affects a baby's platelets. This can put them at risk of problems with bleeding, particularly into the brain. One baby per week in the UK may be seriously affected and milder forms can affect one in every 1000 births. HOW IS IT CAUSED?: Platelets are blood cells that are very important in helping blood to clot. All platelets have natural proteins on their surface called human platelet antigens (HPAs). In babies, half of these antigens are inherited from the mother and half from the father. During pregnancy, some of the baby's platelets can cross into the mother's bloodstream. In most cases, this does not cause a problem. But in cases of FNAIT, the mother's immune system does not recognise the baby's HPAs that were inherited from the father and develops antibodies, which can cross the placenta and attack the baby's platelets. These antibodies are called anti-HPAs, and the commonest antibody implicated is anti-HPA-1a, but there are other rarer antibody types. If this happens, the baby's platelets may be destroyed causing their platelet count to fall dangerously low. If the platelet count is very low there is a risk to the baby of bleeding into their brain before they are born. This is very rare but if it happens it can have serious effects on the baby's health. HOW IS IT INHERITED?: A baby inherits half of their HPAs from its mother and half from its father. Consequently, a baby may have different HPAs from its mother. As the condition is very rare, and even if the baby is at risk of the condition we have no way of knowing how severely they will be affected, routine screening is not currently recommended. WHAT CAN BE DONE?: FNAIT is usually diagnosed if a previous baby has had a low platelet count. The parents are offered blood tests and the condition can be confirmed or ruled out. There are many other causes of low platelets in babies, which may also need to be tested for. As the condition is so rare, expertise is limited to specialist centres and normally a haematologist and fetal medicine doctor will perform and interpret the tests together. Fortunately, there is an effective treatment for the vast majority of cases called immunoglobulin, or IVIg. This 'blood product' is given intravenously through a drip every week to women at risk of the condition. It may be started from as early as 16 weeks in the next pregnancy, until birth, which would be offered at around 36-37 weeks. Less common treatments that may be considered depending on individual circumstances include steroid tablets or injections, or giving platelet transfusions to the baby. WHAT DOES THIS PAPER TELL YOU?: This paper considers the latest evidence in relation to treatment options in the management of pregnancies at risk of FNAIT. Specifically, we discuss the role of screening, when IVIg should be started, what dose should be used, and what evidence there is for maternal steroids. We also consider in very rare selected cases, the use of fetal blood sampling and giving platelet transfusions to the baby before birth. Finally, we consider the approaches to blood testing mothers to tell if babies are at risk, which is offered in some countries, and development of new treatments to reduce the risk of FNAIT.


Assuntos
Doenças Fetais/genética , Imunoglobulinas Intravenosas/uso terapêutico , Doenças do Recém-Nascido/genética , Programas de Rastreamento/métodos , Cuidado Pré-Natal/métodos , Trombocitopenia Neonatal Aloimune/diagnóstico , Trombocitopenia Neonatal Aloimune/prevenção & controle , Antígenos de Plaquetas Humanas , Feminino , Doenças Fetais/prevenção & controle , Doenças Fetais/terapia , Testes Genéticos , Humanos , Recém-Nascido , Doenças do Recém-Nascido/terapia , Anamnese , Contagem de Plaquetas , Gravidez , Trombocitopenia Neonatal Aloimune/genética , Trombocitopenia Neonatal Aloimune/terapia
6.
Taiwan J Obstet Gynecol ; 58(2): 251-254, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30910148

RESUMO

OBJECTIVE: To investigate the clinical value of chromosomal microarray analysis (CMA) in the prenatal diagnosis of genetic abnormalities in fetal isolated mild ventriculomegaly. MATERIALS AND METHODS: This retrospective study reviewed 101 fetuses with isolated mild ventriculomegaly who had undergone invasive prenatal diagnosis at our hospital. CMA was performed in all cases to detect chromosomal aneuploidy as well as copy number variations (CNVs) that are too small to be detected by conventional karyotyping. Real time quantitative PCR (qPCR) or multiplex ligation dependent probe amplification (MLPA) was used to confirm all fetal CNVs <400 Kb. RESULTS: Except for three cases of chromosomal aneuploidy, CMA revealed pathogenic copy number variations (CNVs) in 3.0% (3/101) of the fetuses; these cases demonstrated involvement in the chromosomal regions 15q11.2, 1q21.1 and Xq27.3q28. Furthermore, we detected three likely pathogenic (3.0%) and two variants of uncertain significance (2.0%) among 101 fetuses diagnosed as isolated mild ventriculomegaly on ultrasound examination. CONCLUSION: Our study suggests that CNVs could aid in the risk assessment and genetic counseling in fetuses with isolated ventriculomegaly.


Assuntos
Variações do Número de Cópias de DNA/genética , Doenças Fetais/diagnóstico , Hidrocefalia/diagnóstico , Análise em Microsséries , Diagnóstico Pré-Natal/métodos , Aneuploidia , Feminino , Doenças Fetais/genética , Idade Gestacional , Humanos , Hidrocefalia/embriologia , Hidrocefalia/genética , Masculino , Gravidez , Estudos Retrospectivos , Medição de Risco
7.
Vox Sang ; 114(4): 386-393, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30834546

RESUMO

BACKGROUND AND OBJECTIVES: Fetal RHD genotyping of cell-free fetal DNA from RhD-negative pregnant women can be used to guide targeted antenatal and postnatal anti-D prophylaxis for the prevention of RhD immunization. To assure the quality of clinical testing, we conducted an external quality assessment workshop with the participation of 28 laboratories. MATERIALS AND METHODS: Aliquots of pooled maternal plasma were sent to each laboratory. One sample was positive, and the second sample was negative for fetal RHD, verified by pre-workshop testing using quantitative real-time PCR (qPCR) analysis of RHD exons 4, 5, 7 and 10. Plasma samples were shipped at room temperature. A reporting scheme was supplied for data collection, including questions regarding the methodological setup, results and clinical recommendations. Different methodological approaches were used, all employing qPCR with a total of eight different combinations of RHD exon targets. The samples were tested blindly. RESULTS: Fetal RHD genotyping was performed with no false-negative and no false-positive results. One inconclusive result was reported for the RHD-positive sample, and four inconclusive results were reported for the RHD-negative sample. All clinical conclusions were satisfactory. CONCLUSION: This external quality assessment workshop demonstrates that despite the different approaches taken to perform the clinical assays, fetal RHD genotyping is a reliable laboratory assay to guide targeted use of Rh prophylaxis in a clinical setting.


Assuntos
Doenças Fetais/prevenção & controle , Reação em Cadeia da Polimerase em Tempo Real , Isoimunização Rh/prevenção & controle , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Imunoglobulina rho(D)/genética , Educação Continuada , Éxons , Feminino , Doenças Fetais/genética , Feto , Genótipo , Humanos , Gravidez , Diagnóstico Pré-Natal/métodos , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade , Qualidade da Assistência à Saúde , Reprodutibilidade dos Testes , Isoimunização Rh/genética , Sistema do Grupo Sanguíneo Rh-Hr/genética , Imunoglobulina rho(D)/sangue , Imunoglobulina rho(D)/química
8.
Hong Kong Med J ; 25(1): 6-12, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30655461

RESUMO

INTRODUCTION: The aim of the present study was to calculate the prevalence of chromosomal abnormalities among antenatally diagnosed congenital heart diseases (CHDs), and the prevalence of 22q11.2 deletion in those with conotruncal CHDs versus isolated non-conotruncal CHDs. METHODS: All patients with antenatal ultrasound finding of fetal CHDs in two obstetric units in a 5-year period were retrospectively reviewed. Detected CHDs were classified as conotruncal if the malformation involved either the aortic outflow tract or the pulmonary outflow tract; otherwise they were classified as non-conotruncal. Karyotyping, fluorescence in situ hybridisation for 22q11.2 deletion (22q11FISH), and array comparative genomic hybridisation (aCGH) results were retrieved from patient medical records. The primary outcome was prevalence of chromosomal abnormalities in CHDs. The secondary outcomes were prevalence of 22q11.2 deletion and its prevalence in conotruncal versus non-conotruncal CHDs. RESULTS: A total of 254 Chinese patients were diagnosed to have fetal CHDs. In all, 50 (19.7%) were found to have chromosomal abnormalities with seven (2.8%) patients having 22q11.2 deletion, of whom all seven had conotruncal CHDs and none had non-conotruncal CHDs (P<0.05). Conventional karyotyping detected 35 (70%) cases of the chromosomal abnormalities. The 22q11FISH detected three cases of 22q11.2 deletion; aCGH was performed to detect four cases of 22q11.2 deletion and eight other cases of copy number variations. CONCLUSION: Our results suggest that invasive testing for karyotyping is recommended for fetal CHDs. Although the prevalence of 22q11.2 deletion was low, testing for 22q11.2 deletion should be offered for conotruncal CHDs.


Assuntos
Síndrome da Deleção 22q11/epidemiologia , Síndrome da Deleção 22q11/genética , Cromossomos Humanos Par 22/genética , Doenças Fetais/genética , Cardiopatias Congênitas/genética , Adulto , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Feminino , Doenças Fetais/epidemiologia , Cardiopatias Congênitas/epidemiologia , Hong Kong/epidemiologia , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Cariotipagem , Gravidez , Resultado da Gravidez , Prevalência , Estudos Retrospectivos , Ultrassonografia Pré-Natal
9.
Eur J Obstet Gynecol Reprod Biol ; 233: 120-126, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30594021

RESUMO

OBJECTIVE: To explore the outcomes and prognostic factors associated with fetal megacystis (enlarged bladder). STUDY DESIGN: The MEDLINE and EMBASE databases were searched for studies reporting on outcomes of fetal megacystis. The outcomes observed were chromosomal abnormalities, associated structural anomalies, spontaneous resolution, and survival rates. We also evaluated the potential role of fetal gender, oligohydramnios, gestational age at diagnosis, and intrauterine intervention as prenatal prognostic factors. RESULTS: The search identified 558 articles in total, and 13 studies (1675 fetuses) were included in this systematic review. The overall incidences of chromosomal abnormalities and associated structural anomalies in fetal megacystis were 10% and 24%, respectively. Spontaneous resolution of megacystis occurred in 32% of fetuses, and 44% of fetuses were born alive and survived until the follow-up. The odds ratio of survival with oligohydramnios was 0.14, and the mean difference in gestational age at diagnosis between survival and non-survival was 3.43 weeks. No significant difference in survival rate was observed between the genders, and an intrauterine intervention did not significantly improve the prognosis. CONCLUSIONS: A considerable proportion of fetuses with megacystis are born with a good prognosis. Oligohydramnios and lower gestational age at diagnosis are associated with worse outcomes.


Assuntos
Duodeno/anormalidades , Doenças Fetais/diagnóstico , Diagnóstico Pré-Natal , Bexiga Urinária/anormalidades , Feminino , Doenças Fetais/genética , Doenças Fetais/mortalidade , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Oligo-Hidrâmnio/diagnóstico , Gravidez , Resultado da Gravidez , Remissão Espontânea , Estudos Retrospectivos
10.
Expert Rev Mol Diagn ; 19(2): 189-196, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30582381

RESUMO

OBJECTIVES: This study was aimed to report the clinical characteristics of fetal chromosomal aneuploidy diseases using noninvasive prenatal testing (NIPT) in twin pregnancies and analyze the results in terms of chorionicity, conception, and fetal fraction. METHODS: A total of 1160 women with twin pregnancies were recruited from 1 October 2015, to 1 August 2017. Next-generation sequencing technology was used to detect fetal aneuploidies, such as trisomy 21, trisomy 18, trisomy 13 and trisomy X. RESULTS: Aneuploidy was detected using NIPT in 26 fetuses, among which 18 fetal aneuploidies occurred in only one fetus of the twins. The rate of aneuploidy was 1.3% for dichorionic diamniotic twins and 0.5% for monochorionic diamniotic twins, respectively. The rate of aneuploidy was 1.2% for spontaneous pregnancy group and 1.1% for assisted reproductive technologies group. CONCLUSION: In this study, detection of trisomy 21, trisomy 18, trisomy 13, and X abnormality in twin pregnancies was confirmed to be accurate. The aneuploidies mostly occurred in only one fetus of the twins, and trisomy 21 was the most common type. The prenatal diagnostic standard for NIPT in singleton pregnancies could perform well in twin pregnancies, which means NIPT can be popularized as routine prenatal screening in twin pregnancies.


Assuntos
Síndrome de Down , Doenças Fetais , Gravidez de Gêmeos , Diagnóstico Pré-Natal , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18 , Trissomia , Cromossomos Humanos X/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Testes Genéticos , Humanos , Gravidez , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , 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
11.
Twin Res Hum Genet ; 21(6): 485-494, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30587273

RESUMO

The Barker hypothesis states that low birth weight (BW) is associated with higher risk of adult onset diseases, including mental disorders like schizophrenia, major depressive disorder (MDD), and attention deficit hyperactivity disorder (ADHD). The main criticism of this hypothesis is that evidence for it comes from observational studies. Specifically, observational evidence does not suffice for inferring causality, because the associations might reflect the effects of confounders. Mendelian randomization (MR) - a novel method that tests causality on the basis of genetic data - creates the unprecedented opportunity to probe the causality in the association between BW and mental disorders in observation studies. We used MR and summary statistics from recent large genome-wide association studies to test whether the association between BW and MDD, schizophrenia and ADHD is causal. We employed the inverse variance weighted (IVW) method in conjunction with several other approaches that are robust to possible assumption violations. MR-Egger was used to rule out horizontal pleiotropy. IVW showed that the association between BW and MDD, schizophrenia and ADHD is not causal (all p > .05). The results of all the other MR methods were similar and highly consistent. MR-Egger provided no evidence for pleiotropic effects biasing the estimates of the effects of BW on MDD (intercept = -0.004, SE = 0.005, p = .372), schizophrenia (intercept = 0.003, SE = 0.01, p = .769), or ADHD (intercept = 0.009, SE = 0.01, p = .357). Based on the current evidence, we refute the Barker hypothesis concerning the fetal origins of adult mental disorders. The discrepancy between our results and the results from observational studies may be explained by the effects of confounders in the observational studies, or by the existence of a small causal effect not detected in our study due to weak instruments. Our power analyses suggested that the upper bound for a potential causal effect of BW on mental disorders would likely not exceed an odds ratio of 1.2.


Assuntos
Doenças Fetais/patologia , Variação Genética , Análise da Randomização Mendeliana/métodos , Transtornos Mentais/etiologia , Modelos Biológicos , Doenças Fetais/genética , Pleiotropia Genética , Humanos , Medição de Risco
12.
Medicine (Baltimore) ; 97(50): e13617, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30558042

RESUMO

BACKGROUND: Congenital heart disease (CHD) is one of the most common birth defects; however, the mechanisms underlying its development are poorly understood. Recently, heritable genetic factors, including copy number variations (CNVs) and single nucleotide polymorphisms (SNPs), have been implicated in its etiology. The aim of this study was to investigate the utility of a SNP array for the prenatal diagnosis of CHD and the improvement of prenatal genetic counseling and to compare this approach to traditional chromosome analysis. METHODS: One hundred and fortysix cases of CHD detected by prenatal echocardiography were analyzed. Of these, 110 were isolated CHD and 36 were of CHD with extracardiac defects. SNP analysis was performed using the Affymetrix CytoScan HD platform, which was followed by karyotype analysis. All annotated CNVs were validated by fluorescence in situ hybridization. RESULTS: Karyotype analysis identified chromosomal abnormalities in 19 of 146 cases. In addition to the 15 chromosomal abnormalities that were consistent with the results of karyotype analysis, the SNP array identified abnormal CNVs in an additional 15.2% (22/145) cases; of these, 15 were pathogenic CNVs, three were variations of uncertain clinical significance, and four were benign CNVs. The rates at which the SNP array detected pathogenic CNVs differed significantly between cases of isolated CHD and CHD with extracardiac defects (13.6% vs. 72.2%, P = .001). The results of the SNP array also affected the rate of pregnancy termination. CONCLUSION: Combining SNP array with cytogenetic analyses is particularly effective for identifying chromosomal abnormalities in CNVs in fetuses with CHD, which also affects obstetrical outcomes.


Assuntos
Análise Citogenética/métodos , Cardiopatias Congênitas , Cariotipagem/métodos , Polimorfismo de Nucleotídeo Único/genética , Diagnóstico Pré-Natal/métodos , China/epidemiologia , Aberrações Cromossômicas , Variações do Número de Cópias de DNA/genética , Ecocardiografia/métodos , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/epidemiologia , Doenças Fetais/genética , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/etiologia , Humanos , Gravidez , Resultado da Gravidez/epidemiologia , Cuidado Pré-Natal/métodos , Reprodutibilidade dos Testes
15.
Taiwan J Obstet Gynecol ; 57(3): 452-455, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29880184

RESUMO

OBJECTIVE: Harlequin ichthyosis (HI) was the most severe form of ichthyoses, which leaded to neonatal death in 50% of cases. It was the result of mutations in ABCA12 gene. With the development of ultrasound skills and genetic analysis, HI could be prenatal diagnosed. CASE REPORT: Here, we reported a case of HI, which was prenatal diagnosed by ultrasound examination and genetic analysis. The fetus was found that severe ectropion, eclabium, flattened nose, and rudimentary ears by ultrasound at 20 weeks gestation. A molecular genetic analysis was performed and revealed two mutations in the ABCA12 gene. One of two mutations were not reported in the past. The fetus was terminated. CONCLUSION: HI was associated with the poor prognosis of HI neonates. Prenatal ultrasound and genetic analysis were important for prenatal diagnosis of HI and were helpful to give sufficient prenatal counsels for the family with HI baby.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Doenças Fetais/genética , Ictiose Lamelar/genética , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/genética , Adulto , Feminino , Doenças Fetais/diagnóstico por imagem , Heterozigoto , Humanos , Ictiose Lamelar/diagnóstico por imagem , Masculino , Mutação , Gravidez , Ultrassonografia Pré-Natal
16.
Medicine (Baltimore) ; 97(15): e0112, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29642139

RESUMO

Although fetal cardiac rhabdomyoma can be the initial finding in patients with tuberous sclerosis complex (TSC), the challenges of precise genetic diagnosis of TSC can now be potentially overcome by new whole or targeted genomic sequencing. The goals of this study were to investigate the correlation between suspected cardiac rhabdomyoma and TSC to provide the information for a prenatal diagnosis of TSC and to validate the TSC genotype in this cohort of fetuses with suspected prenatal cardiac rhabdomyoma.We retrospectively analyzed 10,728 fetal echocardiograms from January 2013 to March 2016 in our institution. A total of 32 fetuses were suspected of having cardiac rhabdomyomas. Among them, 15 subjects met the inclusion criteria and provided written consent. Samples from fetuses (n = 13 after terminations) and newborns (n = 2) were available for targeted genomic sequencing of the exons and introns of the TSC1 and TSC2 genes and the adjacent 10 base pairs and for validated studies using Sanger sequencing.Among the 15 subjects with suspected cardiac rhabdomyoma and TSC genomic sequencing data, 7 subjects were familial and 8 subjects were sporadic cases. Fetal echocardiography showed a single tumor in 2 fetuses and multiple tumors in 13 fetuses. Gene sequencing analysis showed no mutation of the TSC1 or TSC2 gene in 2 subjects with a single tumor but positive mutations in all 13 subjects with multiple tumors. Among the latter, 5 mutations were "pathogenic" and have been previously reported (4 familial and 1 sporadic). Six new mutations were "likely pathogenic" and had not been previously reported (3 familial and 3 sporadic); 1 was of "uncertain significance" (sporadic), and 1 was suspected of being "likely benign" (sporadic).Prenatal suspected cardiac rhabdomyoma detected by fetal echocardiography should raise the suspicion of TSC. In fetuses with multiple tumors, especially the familial cases, genomic sequencing has a high yield of detecting TSC-causing genes. Patient history, prenatal fetal echocardiography, and targeted genomic sequencing may facilitate screening for, diagnosis of, and counseling for TSC.


Assuntos
Neoplasias Cardíacas , Diagnóstico Pré-Natal/métodos , Rabdomioma , Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética , Ecocardiografia/métodos , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/etiologia , Neoplasias Cardíacas/patologia , Humanos , Recém-Nascido , Imagem por Ressonância Magnética/métodos , Masculino , Mutação , Gravidez , Estudos Retrospectivos , Rabdomioma/diagnóstico , Rabdomioma/etiologia , Rabdomioma/patologia , Análise de Sequência de DNA/métodos , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa
17.
Cell Physiol Biochem ; 45(6): 2483-2496, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29554656

RESUMO

BACKGROUND/AIMS: Published studies indicated that the MTHFR gene polymorphisms C677T and A1298C are associated with congenital heart disease (CHD) risk in children, but obtained inconsistent results. Our study aims to reach a more accurate association between these two polymorphisms and CHD risk. METHODS: Eligible studies were obtained by screening the PubMed, Embase, China National Knowledge Infrastructure, Wan Fang and VIP databases based on designed searching strategy. The odds ratio (OR) and 95% confidence interval (CI) were calculated. Moreover, a trial sequential analysis was introduced to confirm the positive results and an RNA secondary structure analysis was also applied to discover the potential molecular mechanism. RESULTS: Based on thirty-two published articles, involving 6988 congenital heart disease subjects and 7579 healthy controls, the pooled results from the C677T polymorphism in the fetal population showed increased risks in allelic model (OR=1.32, 95%CI=1.14-1.53), recessive model (OR=1.69, 95%CI=1.25-2.30), dominant model (OR=1.35, 95%CI=1.11-1.64), heterozygote model (OR=1.20, 95%CI=1.01-1.41) and homozygote model (OR=1.75, 95%CI=1.31-2.33). An increased risk was only detected in the A1298C polymorphism in the overall fetal popalation in a recessive model (OR=1.42, 95%CI=1.10-1.84). In the subgroup stratified by region, sample size, genotyping method and source of controls, the increased risks were widely observed in both the C677T and A1298C polymorphisms with CHD risk. Furthermore, trial sequential analysis confirmed our positive results, and the RNA secondary structure analysis detected the changes in the RNA secondary structure caused by the mutant 677T allele and 1298C allele. CONCLUSION: In summary, we found that the MTHFR C677T polymorphism is associated with a significant increased risk in congenital heart disease in the fetal population. Moreover, an increased risk in the CC genotype of MTHFR A1298C polymorphism was observed, but the protective role of the 1298C allele needs further study.


Assuntos
Doenças Fetais/genética , Cardiopatias Congênitas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Alelos , Doenças Fetais/epidemiologia , Predisposição Genética para Doença , Genótipo , Cardiopatias Congênitas/epidemiologia , Humanos , Fatores de Risco
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(1): 51-55, 2018 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-29419860

RESUMO

OBJECTIVE To assess the performance of non-invasive prenatal testing (NIPT) based on massive parallel sequencing. METHODS A total of 10 275 maternal blood samples were collected. Fetal chromosomal aneuploides were subjected to low coverage whole genome sequencing. Patients with high risks received further prenatal diagnosis. The outcome of all patients were followed up. RESULTS High-throughput sequencing detected 72 pregnancies with fetal autosomal chromosomal aneuploidy, including 57 cases of trisomy 21, 14 cases of trisomy 18, and 1 case of trisomy 13. The positive predictive value for trisomies 21 and 18 were 98.25% and 91.67%, respectively. Comparing its performance in intermediate or high risk pregnancies, advanced maternal age pregnancies and volunteering to test pregnancies, the positive predictive value were 100%, 95%, 90% and 50%, respectively. The follow up result was only 1 case of 21 trisomy false negative with high risk. For the 56 cases of trisomy 21, the high risk group accounted for 55%, advanced maternal age accounted for 29%, the intermediate risk referred to 14%, the volunteering to test group accounted for 2%. CONCLUSION The performance of NIPT for trisomies 21, 18 and 13 was satisfactory. The method can be used for women with advanced gestational age. NIPT has offered an ideal secondary screening method for those with an intermediate or high risk, and can reduce the rate of birth defects.


Assuntos
Transtornos Cromossômicos/genética , DNA/genética , Doenças Fetais/genética , Diagnóstico Pré-Natal/métodos , Adulto , Transtornos Cromossômicos/diagnóstico , DNA/sangue , DNA/química , Feminino , Doenças Fetais/diagnóstico , Idade Gestacional , Humanos , Pessoa de Meia-Idade , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Trissomia/diagnóstico , Trissomia/genética , Sequenciamento Completo do Genoma/métodos , Adulto Jovem
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(1): 60-63, 2018 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-29419862

RESUMO

OBJECTIVE To assess the value of BAC-on-Beads(BoBs) technology combined with conventional chromosomal karyotyping for reducing birth defects. METHODS For 690 women with singleton pregnancy and indication for prenatal diagnosis, aneuploidies of chromosomes 13, 18, 21, X and Y, in addition with 9 microdeletions and microduplications, were detected with the BoBs assay. And the results were compared with that of conventional karyotyping of amniocytes. RESULTS Karyotyping analysis attained a positive rate of 6.08% (42/690), which included 36 aneuploidies and 6 structural aberrations. The BoBs assay attained a detection rate of 5.95% (41/689). In addition to all chromosomal aneuploidies detected by conventional karyotyping, the Bobs assay has detected 3 cases with Xp22 region microdeletions, 1 case with 22q11 segment duplication, and 1 case with 5p15 microduplication. No balanced translocation or chromosomal polymorphisms was detected. CONCLUSION BoBs technique combined with conventional karyotyping is suitable for rapid diagnosis of a large number of prenatal cases and increasing the detection rate for fetal chromosomal abnormalities.


Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/genética , Duplicação Cromossômica , Doenças Fetais/genética , Diagnóstico Pré-Natal/métodos , Adulto , Transtornos Cromossômicos/diagnóstico , Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 5/genética , Cromossomos Humanos X/genética , Feminino , Doenças Fetais/diagnóstico , Humanos , Cariotipagem , Pessoa de Meia-Idade , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
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