Prenatal Diagnosis Of Fetus Research Articles

Prenatal Diagnosis of Central Nervous System Anomalies by High-Resolution Chromosomal Microarray Analysis.

The aims of this study were to evaluate the contribution of chromosomal microarray analysis (CMA) in the prenatal diagnosis of fetuses with central nervous system (CNS) anomalies but normal chromosomal karyotype. A total of 46 fetuses with CNS anomalies with or without other ultrasound anomalies but normal karyotypes were evaluated by array-based comparative genomic hybridisation (aCGH) or single-nucleotide polymorphism (SNP) array. The result showed that CNVs were detected in 17 (37.0%) fetuses. Of these, CNVs identified in 5 (5/46, 10.9%) fetuses were considered to be likely pathogenic, and CNVs detected in 3 (3/46, 6.5%) fetuses were defined as being of uncertain clinical significance. Fetuses with CNS malformations plus other ultrasound anomalies had a higher rate of pathogenic CNVs than those with isolated CNS anomalies (13.6% versus 8.3%), but there was no significant difference (Fisher's exact test, P > 0.05). Pathogenic CNVs were detected most frequently in fetuses with Dandy-Walker syndrome (2/6, 33.3%) when compared with other types of neural malformations, and holoprosencephaly (2/7, 28.6%) ranked the second. CMA is valuable in prenatal genetic diagnosis of fetuses with CNS anomalies. It should be considered as part of prenatal diagnosis in fetuses with CNS malformations and normal karyotypes.

Prenatal Diagnosis of Fetus with Short Limbs Caused by Three Abnormal Chromosomes Inherited from Parents

Prenatal Diagnosis of Fetus with Short Limbs Caused by Three Abnormal Chromosomes Inherited from Parents

Desenvolvimento e mensuração do diâmetro transversal do cerebelo fetal por ressonância magnética

The fetal magnetic resonance imaging (MRI) is an effective method in the prenatal evaluation of normal brain morphology and diagnosis of diseases of the central nervous system. It is an important complement to clinical ultrasound. The cerebellum is one of the least affected structures in cases of fetal growth restriction, so it is a good index for evaluating the fetal development and gestational age. Thus, the biometric evaluation is essential in fetal prenatal diagnosis of brain development. Purpose – Evaluation of the transversal cerebellum diameter (the anatomical structures reference of fetal central nervous system) and compare it with an international reference study in this regard. Material and methods – The sample consisted of 84 pregnant women who have performed magnetic resonance in a medical imaging clinic in the Centre region. The average considered for evaluating the fetal development was the transversal cerebellum diameter. Results – The results for the transversal cerebellum diameter demonstrate the absence of statistically significant mean differences (p>0.05) in the number of weeks of gestation compared with theoretical values measured in the study by Garel. Conclusion – Based on the obtained results we can conclude that the parameter analyzed is consistent with the publication of Catherine Garel – Le developpement du cerveau foetal atlas IRM et biometrie.

Prenatal diagnosis of maternally inherited X-linked Opitz G/BBB syndrome by chromosomal microarray in a fetus with complex congenital heart disease

BackgroundPrenatal sonographic diagnosis of Optiz G/BBB syndrome is difficult because the common clinical features, such as hypertelorism, hypospadias and abnormalities of midline structures, including laryngotracheoesophageal defects, are subtle. MethodChromosomal microarray (CMA) analysis using a target enriched Fetal DNA Chip design was performed on the DNA of a fetus with congenital cardiac abnormalities. ResultsFetal DNA chip revealed a 48Kb single copy number loss within chromosome region Xp22.2 (arr[hg18]Xp22.2(10,627,354–10,675,946)x0 mat). This deletion included the 3′ UTR region of the MID1 gene predicted to cause the X-linked Opitz G/BBB syndrome. ConclusionsThis case supports the use of CMA in prenatal diagnosis of fetuses with congenital heart disease. CMA allows prenatal diagnosis of genomic aberrations at a much higher resolution compared with conventional karyotyping, and such findings enable proper genetic counseling and decision making in the pregnancy.

Prenatal Diagnosis of Fetus with Short Limbs Caused by Three Abnormal Chromosomes Inherited from Parents

A 29 year old woman with history of G2P0+1 and shortening of limbs in past pregnancy referred herself to undergo a fetal anomaly scan at 18th week of gestation. The ultrasonographic imaging of the present pregnancy admeasuring the growth of 12-13 weeks at 18th week detected hydrocephalous condition with short limbs and kyphotic spine. This report aimed at looking for chromosomal aberrations in association with the imaging results and discussed the case in light of available literature. Amniocentesis and conventional cytogenetic analysis was performed following the standard protocol of tissue culture and chromosome banding. Karyotypic analysis of 50 metaphases detected an abnormal female karyotype with 46,XX,inv(9)(p11q13),t(15;16)(q15;q22) pattern. The karyotype revealed two constitutive abnormalities involving four break-points on three different chromosomes in a female genome. Upon counseling, the parents decided to terminate the pregnancy. However, at delivery the external genitalia of the female fetus was found to be of male phenotype and ambiguous. Parental karyotyping revealed transmission of inversion from mother and the balanced translocation from father. Finally the fetal karyotype was expressed as 46,XX,inv(9)(p11q13)mat,t(15;16)(q15;q22)pat.

Prenatal Diagnosis of Fetus in Fetu with a Well Formed Skull: A Rare Case Report

Fetus in fetu is an extremely rare condition embryologically arising in monozygotic diamniotic twins with an incidence of 1:500,000 births. To the best of our knowledge, number of reported cases should not be more than 100 with majority of cases presenting in post natal life with only 5 cases detected prenatally. We are presenting a case diagnosed at 24 weeks of gestation on ultrasound with presence of well formed skull, facial skeleton and bony orbit.

P11.09: Prenatal diagnosis of fetus in fetus (FIF) with MRI and biopsy confirmation

<scp>P11</scp>.09: Prenatal diagnosis of fetus in fetus (<scp>FIF</scp>) with <scp>MRI</scp> and biopsy confirmation

De la observación microscópica de los cromosomas en el cariotipo a los array-CGH en el diagnóstico prenatal

Introducción: el cariotipo ha sido la prueba de oro para el análisis cromosómico en el diagnóstico prenatal en los últimos cuarenta años; sin embargo, a partir del 2011 se publican múltiples artículos y los primeros meta-análisis que muestran posibles ventajas de los array-CGH (del inglés array-comparative genomic hibridization) sobre el cariotipo en el diagnóstico prenatal.Objetivo: hacer una reflexión acerca del uso de array-CGH en el diagnóstico prenatal y mostrar algunas de las potenciales ventajas y desventajas de esta prueba molecular con relación al cariotipo, así como su aplicación por obstetras, perinatólogos y especialistas en medicina materno-fetal.Conclusión: los a-CGH son una nueva alternativa en el análisis cromosómico en el diagnóstico prenatal en fetos con anomalías anatómicas; pueden usarse en todos los casos en que se justifique una intervención invasiva en el diagnóstico prenatal de alteraciones cromosómicas, y es probable que los array-CGH reemplacen al cariotipo en el diagnóstico prenatal en esta década.

Rapid prenatal genetic diagnosis of a fetus with a high risk for Morquio A syndrome

To provide rapid and accurate prenatal genetic diagnosis for a fetus with high risk of Morquio A syndrome. Based on ascertained etiology of the proband and genotypes of the parents, particular mutations of the GALNS gene were screened at 10th gestational week with amplification refractory mutation system (ARMS), denaturing high performance liquid chromatography (DHPLC), and direct DNA sequencing. DHPLC screening has identified abnormal double peaks in the PCR products of exons 1 and 10, whilst only a single peak was detected in normal controls. Amplification of ARMS specific primers derived a specific product for the fetus's gene, whilst no similar product was detected in normal controls. Sequencing of PCR products confirmed that exons 1 and 10 of the GALNS gene from the fetus contained a heterozygous paternal c.106-111 del (p.L36-L37 del) deletion and a heterozygous maternal c.1097 T>C (p.L366P) missense mutation, which resulted in a compound heterozygote status. The fetus was diagnosed with Morquio A syndrome and a genotype similar to the proband. Termination of the pregnancy was recommended. Combined ARMS, DHPLC and DNA sequencing are effective for rapid and accurate prenatal diagnosis for fetus with a high risk for Morquio A syndrome. Such methods are particularly suitable for early diagnosis when pathogenesis is clear. Furthermore, combined ARMS and DHPLC are suitable for rapid processing of large numbers of samples for the identification of new mutations.

Non‐targeted whole genome 250K SNP array analysis as replacement for karyotyping in fetuses with structural ultrasound anomalies: evaluation of a one‐year experience

We evaluated both clinical and laboratory aspects of our new strategy offering quantitative fluorescence (QF)-PCR followed by non-targeted whole genome 250K single-nucleotide polymorphism array analysis instead of routine karyotyping for prenatal diagnosis of fetuses with structural anomalies. Upon the detection of structural fetal anomalies, parents were offered a choice between QF-PCR and 250K single-nucleotide polymorphism array analysis (QF/array) or QF-PCR and routine karyotyping (QF/karyo). Two hundred twenty fetal samples were included. In 153/220 cases (70%), QF/array analysis was requested. In 35/153 (23%), an abnormal QF-PCR result was found. The remaining samples were analyzed by array, which revealed clinically relevant aberrations, including two known microdeletions, in 5/118 cases. Inherited copy number variants were detected in 11/118 fetuses, copy number variants with uncertain clinical relevance in 3/118 and homozygous stretches in 2/118. In 67/220 (30%) fetuses, QF/karyo was requested: 23/67 (34%) were abnormal with QF-PCR, and in 3/67, an abnormal karyotype was found. Even though QF/array does not reveal a high percentage of submicroscopic aberrations in fetuses with unselected structural anomalies, it is preferred over QF/karyo, as it provides a whole genome scan at high resolution, without additional tests needed and with a low chance on findings not related to the ultrasound anomalies.

Fetal thyroid in two-dimensional ultrasonography: nomograms according to gestational age and biparietal diameter

To establish fetal thyroid nomograms based on gestational age and biparietal diameter and to compare obtained results with previously published data. A cross-sectional study of 241 healthy pregnant women at 14-38 week of gestation was undertaken. Exclusion criteria were: known maternal thyroid or systemic disease, unknown date of last menstrual period, multiple pregnancy and fetal malformations. Fetal thyroid diameter (FTD), circumference (FTC) and area (FTA) were measured by two-dimensional ultrasonography and plotted against gestational age (GA) and biparietal diameter (BPD). FTD, FTC and FTA increased logarithmically to GA and BPD. Fetal thyroid measurements as a function of GA were expressed by logarithmic formulas: ln(FTD)=3.6025-23.0315/GA, ln(FTC)=4.6227-22.8003/GA, ln(FTA)=6.6303-45.0831/GA. The following logarithmic formulas were obtained for fetal thyroid measurements according to BPD: ln(FTD)=3.4068-45.4271/BPD, ln(FTC)=4.4271-44.8359/BPD, ln(FTA)=6.2390-88.4408/BPD. There were highly significant correlations between thyroid measurements and GA or BPD: r=0.87-0.90, p<0.00001. We have established age-dependent and age-independent nomograms of fetal thyroid. These nomograms will enable prenatal diagnosis in fetuses at risk of thyroid disorders.

Prenatal diagnosis in congenital heart disease of 22q11 microdeletion

Objective To explore the necessity and feasibility of the prenatal diagnosis of 22q11 microdeletion in fetuses with congenital heart disease.Methods Amniocentesis or cordocentesis were used to get the cells of fetuses in 16 pregnant women tested as fetal congenital heart defects by prenatal ultrasound examination.Then the karyotype analysis and two-color fluorescence in situ hybridization were all carried out for detection of 22q11 microdeletion in these fetuses.Results 22q11 microdeletion was detected in I case.Conclusion 22q1 1 microdeletion prenatal diagnosis in fetuses with congenital heart disease is neccessary and feasible.It has great significance for avoiding the birth of children with congenital heart disease caused by 22q11 microdeletion and recurrence birth risk assessment. Key words: 22q11 microdeletion; Fluorescence in situ hybridization; Congenital heart disease; Prenatal diagnosis

Diagnostic value of echocardiographic detection in the differentiation of normal and coarctation of the aorta in fetuses

Objective To establish normal reference indexes of aorta during gestation and cut-points for detection of fetuses with coarctation of aorta.Methods From long-axis views of the aortic arch,the internal diameter of the aortic root,ascending aorta,transverse aortic arch,aortic isthmus,descending aorta,anonyma,left common carotid artery,left subclavian artery were measured in 234 normal fetuses at different time ranging from 14 to 41 weeks during gestation.Reference values of each aortic segment were constructed by linear regression analysis.The ratio of each aortic segment to the ascending aorta were calculated.ResultsThe internal diameter in each aortic segments increased as pregnancy progressed (P<0.01).In the prenatal diagnosis of fetus with coarctation of the aorta,the ratio of the aortic isthmus to the ascending aorta and descending aorta to the ascending aorta were significantly lower than the normal fetuses(all P<0.01).Conclusions The ratio of the aortic isthmus to the ascending aorta and ratio of descending aorta to the ascending aorta detected by echocardiography may be helpful in the prenatal diagnosis of coarctation of aorta. Key words: Ultrasonography,prenatal; Aorta; Aortic coarctation

일 대학병원 간호사의 생명의료윤리(biomedical ethics)적 가치관

This study was conducted to identify the bioethical attitude of nurses working in a tertiary hospital. Data were collected from 208 nurses who agreed to participate in the study and analyzed by descriptive statistics, t-test, ANOVA and Scheffé test, and pearson’s correlation. Mean score of bioethical attitude of the subjects was 2.88±0.23 and slightly took up for the position of deontology. Especially, in the areas of right to life fetus, organ transplantation, right to life newborn, artificial insemination, artificial abortion, and euthanasia were more took up for the position of deontology than brain death and human biotechnology. Those who were older,moderate economic level, firm ethical attitudes, the intent to attend class on biomedical ethics, and the possibility of increasing ethical problems according to the development of the life science took up for more deontological position than those who were not. In addition, in the areas of right to life fetus, prenatal diagnosis of fetus, right to life newborn, euthanasia, artificial insemination,organ transplantation, human biotechnology, brain death, and artificial abortion were all significantly correlated each other.

Prenatal diagnosis of a fetus in a family with mandibulofacial dysostosis

To measure the feasibility of application of comparative genomic hybridization technique in the prenatal diagnosis of fetus with mandibulofacial dysostosis. A pregnant woman having a fetus with mandibulofacial dysostosis diagnosed by prenatal ultrasound test was selected. The amniotic fluid and blood of the pregnant and blood of her husband were collected and conventional cytogenetic analysis was performed. The whole genome was scanned by array comparative genomic hybridization assay (array-CGH). Reverse transcription fluorescence quantitative PCR (RT-qPCR) analysis was used to verify the result of array-CGH. No abnormality was found in conventional cytogenetic analysis while a duplicated region in 1p36.33 was detected by array-CGH assay. The region spans 722 kb and contains two genes, VWA1 and PYGO2, which play roles in the development of cartilage. The result of array-CGH was confirmed by the RT-qPCR assay. The diagnosis of mandibulofacial dysostosis was confirmed after birth. Author diagnosed a fetus with mandibulofacial dysostosis by array-CGH assay and found two candidate genes related to the development of craniofacial bone: VWA1 and PYGO2.

Ultra-sonografia pré-natal no diagnóstico de aneurisma da veia de Galeno.

Vein of Galen aneurysm is a rare congenital anomaly, originated from a defect in fusion of internal cerebral veins. Due to low resistance, it produces high debit cardiac insufficiency. It constitutes 1% of all intracranial vascular malformations. Prognosis depends on patient's age when the manifestation occurs and aneurysm size. The two reported cases are about fetal prenatal diagnosis of vein of Galen aneurysm, confirmed by ultrasonography, which evolved for caesarian delivery at term gestation. Magnetic resonance was carried out after birth, confirming prenatal diagnosis. The first patient had spontaneous thrombosis of the aneurysm while the second was submitted to embolization. Both of them had hospital discharge with ambulatory accompaniment. The prenatal ultrasonography diagnosis is fundamental to determine aneurysm size, defining the best treatment, when this procedure is indicated, and the more adequate obstetric and perinatal assistance.

Influence of balanced chromosomal structure abnormality on the fertility

Objective To study the influence of balanced chromosomal structure abnormality on the fertility. Methods Karyotype of 1481 fertility abnormality patients were analyzed by chromosome G handing. The carriers of balanced chromosomal structure abnormality continue pregnancy to 16 weeks after the heredity consultation, the birth instruction and ART treatment; accept the amniotic fluid or the fetal blood chromosome prenatal diagnostics, Results 52 carriers of balanced chromosomal structure abnormality were detected, the abnormal incidence was 3.51%. 23 amniotic fluids or the fetal blood chromosome prenatal diagnosis picks out 4 non-balanced chromosome abnormalities, 9 balanced chromosomal structure abnormalities and 10 chromosome normal embryos, inv(9) picks out rote is 0.95%, close 1% crowd formation rate. Conclusions ① The male chromosomal structure abnormalities mainly causes to male spermatogenesis dysfunction and infertility. ② After the heredity consultation, to give the fertility instruction and ART treatment, the carriers of balanced chromosomal structure abnormalities would be possible to birth the phenotype normal descendant, in has the prenatal diagnosis technology to make the safeguard under the premise.③ inv(9) does not have unhealthy influence of fertility, does not have the pathology significance. Key words: Chromosome; Fertility; Heredity consultation; Prenatal diagnosis

Diagnosing Chromosomal Abnormalities From “Big” to “Small” With Molecular Cytogenetic Technology

We reviewed the available molecular cytogenetic techniques and their potential use in prenatal diagnosis of fetuses with multiple congenital anomalies and a “normal” standard chromosomal karyotype. We searched Medline to identify reports published after 1995 that were related to molecular prenatal diagnosis. After review, we reached the following conclusions:1.In fetuses with a normal standard karyotype result, common chromosomal microdeletion syndromes may be suspected based on the pattern of congenital anomalies seen on prenatal ultrasound.2.When a microdeletion syndrome is suspected based on the pattern of fetal anomalies, FISH testing for the specific molecular locus should be undertaken.3.Routine chromosome analysis, which has been the gold standard for prenatal cytogenetic diagnosis, may in the future be replaced by microarray technology with increased diagnostic capability for smaller, submicroscopic genetic alterations associated with postnatal morbidity.4.Microarray technology has been shown to increase our ability to make a diagnosis of known or new chromosomal deletion syndromes in pediatric populations with developmental delay. The use of this technology for prenatal diagnosis is currently limited but is likely to expand.

Evaluation of prenatal‐onset osteochondrodysplasias by ultrasonography: A retrospective and prospective analysis

The osteochondrodysplasias or skeletal dysplasias are a heterogenous group of over 350 distinct disorders of skeletogenesis. Many manifest in the prenatal period, making them amenable to ultrasound prenatal diagnosis. A retrospective analysis evaluated 1,500 cases referred to the International Skeletal Dysplasia Registry (ISDR) to determine the relative frequency of specific osteochondrodysplasias and correlation of ultrasound versus radiographic diagnoses for these disorders. Within the retrospective cohort of 1,500 cases, 85% of the referred cases represented well-defined skeletal dysplasias, and the other 15% of cases were a mixture of genetic syndromes and probable early-onset intrauterine growth restriction. The three most common prenatal-onset skeletal dysplasias were osteogenesis imperfecta type 2, thanatophoric dysplasia and achondrogenesis 2, accounting for almost 40% of the cases. In a prospective analysis of 500 cases using a standardized ultrasound approach to the evaluation of these disorders, the relative frequencies of osteogenesis imperfecta type 2, thanatophoric dysplasia and achondrogenesis 2 were similar to the retrospective analysis. This study details the relative frequencies of specific prenatal-onset osteochondrodysplasias, their heterogeneity of prenatal-onset skeletal disorders and provides a standardized prenatal ultrasound approach to these disorders which should aid in the prenatal diagnosis of fetuses suspected of manifesting skeletal dysplasias.

Prenatal diagnosis for fetus with hemophilia A

To study the prenatal genetic diagnostic methods for hemophilia A fetus. From 2002 to 2006, 19 hemophilia A families were diagnosed either by long distance-polymerase chain reaction (LD-PCR) for factor VIII intron 22 inversion or by the DNA polymorphism genetic linkage analysis of factor VIII in the Beijing Chaoyang Hospital. (1) Totally 19 women, with 22 pregnancies received the prenatal diagnosis of fetal hemophilia A. The average week at diagnosis was 23 (17-34 ) weeks. All the direct fetal blood sampling (DFBS) were successful. There was no fetal-loss caused by the procedures. (2) Of the 19 hemophilia A families, 14 appeared to be factor VIII intron 22 inversion, in which 16 prenatal diagnoses were done, 10 fetuses were diagnosed as genetical hemophilia A patients, and 6 fetuses were normal. (3) Using combined polymorphism genetic linkage analysis 6 prenatal diagnoses were done, including one woman's two pregnancies, in which both her fetuses were diagnosed as genetical hemophilia A patients. (4) Factor VIII levels of 16 fetuses were measured, and 6 fetuses were unmeasured either because the pregnancy weeks were lower than 20 weeks or the parents refused. Factor VIII level ranged from 0 to 198%. There were 11 fetuses whose factor VIII levels were lower than 10%. Ten of them were diagnosed to be genetical hemophilia A patients, and in only one boy the factor VIII level was 2%, but the genetic diagnosis was normal and for one year's follow up he was doing normal. LD-PCR combined with polymorphism genetic linkage analysis enables a quick and correct detection of hemophilia A carrier. For a carrier pregnancy, prenatal diagnosis could be done for the male fetus. Factor VIII deficiency of the fetus could help make the diagnosis but the final diagnosis should be based on genetic evidence.