The discovery of cell-free fetal DNA (cff-DNA) in maternal plasma offered a new way to noninvasive prenatal diagnosis for single gene disorders. In the past decade, many techniques such as real-time PCR, pyrophosphorolysis-activated polymerization, mass spectrum and digital PCR have been developed for noninvasive prenatal diagnosis. In this review, the author discuss the principles, applications, advantages and disadvantages of these techniques.
DNA ; blood ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Diseases, Inborn ; diagnosis ; genetics ; Humans ; Maternal-Fetal Exchange ; Pregnancy ; Prenatal Diagnosis ; methods

OBJECTIVETo review the role of epigenetic regulation in neonatal diseases and better understand Barker's "fetal origins of adult disease hypothesis".

DATA SOURCESThe data cited in this review were mainly obtained from the articles published in Medline/PubMed between January 1953 and December 2009.

STUDY SELECTIONArticles associated with epigenetics and neonatal diseases were selected.

RESULTSThere is a wealth of epidemiological evidence that lower birth weight is strongly correlated with an increased risk of adult diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular disease. This phenomenon of fetal origins of adult disease is strongly associated with fetal insults to epigenetic modifications of genes. A potential role of epigenetic modifications in congenital disorders, transient neonatal diabetes mellitus (TNDM), intrauterine growth retardation (IUGR), and persistent pulmonary hypertension of the newborn (PPHN) have been studied.

CONCLUSIONSAcknowledgment of the role of these epigenetic modifications in neonatal diseases would be conducive to better understanding the pathogenesis of these diseases, and provide new insight for improved treatment and prevention of later adult diseases.

DNA Methylation ; Diabetes Mellitus ; genetics ; Epigenesis, Genetic ; Fetal Growth Retardation ; genetics ; Genomic Imprinting ; Histones ; metabolism ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; genetics ; Persistent Fetal Circulation Syndrome ; genetics

Preimplantation genetic diagnosis is a very early form of prenatal diagnosis aimed at eliminating embryos carrying serious genetic diseases before implantation. The basic techniques currently used involve embryo biopsy, the polymerase chain reaction and fluorescence in situ hybridization. In the current review, a number of problems arising from the use of these technologies as well as the possible solutions and new developments are discussed.
Cytogenetic Analysis ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Pregnancy ; Preimplantation Diagnosis ; Primed In Situ Labeling

Female ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; genetics ; Maternal-Fetal Relations

Diseases in Twins ; Erythroblastosis, Fetal ; genetics ; Female ; Humans ; Infant, Newborn ; MNSs Blood-Group System ; immunology

OBJECTIVE: To explore the genetic basis for a fetus with Cardiac-urogenital syndrome (CUGS). METHODS: A fetus with congenital heart disease identified at the Maternal Fetal Medical Center for Fetal Heart Disease, Beijing Anzhen Hospital Affiliated to Capital Medical University in January 2019 was selected as the study subject. Clinical data of the fetus was collected. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. RESULTS: Detailed fetal echocardiographic examination had revealed hypoplastic aortic arch. The results of trio-WES revealed that the fetus has harbored a de novo splice variant of the MYRF gene (c.1792-2A>C), for which both parents were of the wild-type. Sanger sequencing confirmed the variant to be de novo. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CNV-seq has identified no chromosomal anomalies. And the fetus was diagnosed with Cardiac-urogenital syndrome. CONCLUSION The de novo splice variant of the MYRF gene probably underlay the abnormal phenotype in the fetus. Above finding has enriched the spectrum of MYRF gene variants.
Female ; Humans ; DNA Copy Number Variations ; Fetal Diseases ; Fetus/abnormalities* ; Heart Defects, Congenital/genetics* ; Mutation ; Transcription Factors/genetics*

OBJECTIVETo explore the application of combined techniques for the prenatal diagnosis of a case with 7q11.23 duplication.

METHODSAmniocentesis was performed in the second trimester for a mother with a high risk suggested by serological prenatal screening. G-banded chromosomal analysis was performed on cultured amniocytes and peripheral blood samples from both parents. DNA from amniotic fluid sample was isolated for a BACs-on-Beads (BoBs) assay. To define the range of duplication, copy number variation was determined with single nucleotide polymorphism array (SNP array, Affymetrix CytoScan 750K) and fluorescence in situ hybridization (FISH) analysis.

RESULTSChromosomal analysis suggested that the fetus and both parents all had a normal karyotype, while a duplication of 7q11.23 was detected by the BoBs assay. SNP array revealed a 1.5 Mb duplication in chromosome 7q11.23, which was confirmed by FISH.

CONCLUSIONCombined prenatal BoBs, SNP array and FISH has enabled effective diagnose of a case with 7q11.23 syndrome.

Adult ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Male ; Middle Aged ; Pregnancy ; Prenatal Diagnosis ; Trisomy ; genetics

OBJECTIVETo track and analyze two false positive cases from non-invasive prenatal testing for potential fetal aneuploidy.

METHODSThe two cases, respectively reported to have XO (+++) and T18 (1/20) XO(+), were analyzed with conventional karyotyping, fluorescence in situ hybridization (FISH) and massively parallel genomic sequencing (MPS).

RESULTSThe first fetus, who was suspected for XO(+++), was verified to have super female syndrome (47,XXX/46,XX) due to confined placental mosaicism by karyotyping of amniotic fluid cells, FISH analysis of placenta and massively parallel sequencing (MPS) of fetal tissue. The second fetus, suspected to have trisomy 18 (1/20) XO(+), was verified to have Turner syndrome by karyotyping, FISH and MPS analyses of umbilical cord blood cells. And the karyotype was 45,X[48]/46, X, der(X) del(X) (p11.21) del(X) (q13.3)[62].

CONCLUSIONNon-invasive prenatal testing carries a risk for false positive diagnosis of fetal sex chromosome and trisomy 18. Combined cytogenetic and molecular techniques are required to ensure an accurate diagnosis.

Adult ; Aneuploidy ; Chromosome Aberrations ; Diagnostic Errors ; False Positive Reactions ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Pregnancy ; Prenatal Diagnosis ; Young Adult

OBJECTIVETo establish a means for prenatal prediction of spinal muscular atrophy (SMA) through survival motor neuron (SMN) gene deletion analysis and genetic counseling in families with a child affected with SMA.

METHODSGenetic analysis for prenatal prediction of Werdnig-Hoffmann disease was performed in a at risk Chinese family by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) in SMN gene exons 7 and 8.

RESULTSThe pregnancy was positive for the homozygous deletion of the SMN gene, thus the fetus was diagnosed as being affected and the pregnancy was terminated.

CONCLUSIONThis approach is fast and reliable for DNA-based prenatal diagnosis of Werdnig-Hoffmann disease.

China ; Female ; Fetal Diseases ; diagnosis ; Gene Deletion ; Genetic Counseling ; Humans ; Pregnancy ; Prenatal Diagnosis ; Spinal Muscular Atrophies of Childhood ; diagnosis ; genetics

Each of us perceives risk differently, and so do our patients. This perception of risk gets even more complex when multiple individuals and interactions are involved: the doctor, the patient-pregnant mother, the spouse-father and the foetus-unborn child. In this review, we address the relationship between different levels of information gathering, from clinical data to experiential knowledge - data, information, knowledge, perception, attitude, wisdom - and how these would impact the perception of risk and informed consent. We discuss how patients might interpret the risks of the same event differently based upon past experiences, and suggest how risk data could be presented more meaningfully for patients and family to assimilate for informed decision making. Finally, we demonstrate how patients' expectations and risk management can impact scientific research and clinical progress by way of the most topical subject of risk screening in pregnancy - non-invasive prenatal testing using cell-free DNA in maternal plasma.
Aneuploidy ; Attitude to Health ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Informed Consent ; psychology ; Pregnancy ; Prenatal Diagnosis ; adverse effects ; psychology ; Risk