OBJECTIVE:: To estimate the accuracy and potential clinical effect of using massively parallel sequencing of maternal plasma DNA to detect fetal aneuploidy in a cohort of pregnant women carrying fetuses with nuchal cystic hygroma. METHODS:: The MatErnal BLood IS Source to Accurately diagnose fetal aneuploidy (MELISSA) study database was queried ...

OBJECTIVE: To assess the performance of cell-free DNA (cfDNA) testing in maternal blood for detection of fetal aneuploidy of chromosomes 13, 18, 21, X, and Y using targeted sequencing of single-nucleotide polymorphisms. METHODS: Prospective study in 242 singleton pregnancies undergoing chorionic villus sampling at 11 to 13 weeks. Maternal blood was ...

BACKGROUND: Advanced maternal age (AMA) is the most frequent indication for amniocentesis in predicting balanced reciprocal translocations, and abnormal ultrasound findings are indications in predicting unbalanced reciprocal translocations; however, to date, no studies have focused on Robertsonian translocations. METHODS: A retrospective review was conducted on 16,749 pregnant women who underwent ...

OBJECTIVE: To report the feasibility of fetal chromosomal deletions/duplications detection by using a novel bioinformatic method of low coverage whole genome sequencing of maternal plasma. METHOD: A practical method FCAPS (Fetal Copy-number Analysis through Maternal Plasma Sequencing), integrated with GC-bias correction, binary segmentation algorithm and dynamic threshold strategy, was developed ...

OBJECTIVE: Whole-genome sequencing of circulating cell free (ccf) DNA from maternal plasma has enabled noninvasive prenatal testing for common autosomal aneuploidies. The purpose of this study was to extend the detection to include common sex chromosome aneuploidies: [47,XXX], [45,X], [47,XXY], and [47,XYY] syndromes. METHOD: Massively parallel sequencing (MPS) was performed ...

Anorectal malformations (ARMs) represent a complex group of congenital anomalies resulting from abnormal development of the hindgut, allantois and Mullerian duct resulting in complete or partial urorectal septal malformations. There is a wide variety of phenotypic expression, ranging from mild anorectal to very complex severe ARM with >75 % having other ...

Purpose:Advanced maternal age and altered recombination are known risk factors for Down syndrome cases due to maternal nondisjunction of chromosome 21, whereas the impact of other environmental and genetic factors is unclear. The aim of this study was to investigate an association between low maternal socioeconomic status and chromosome 21 ...

OBJECTIVE: To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service. METHODS: Five cases with secondary findings were reviewed. RESULTS: In Case 1, NIPT revealed a large duplication in chromosome 18p, which was supported by arrayCGH ...

We present perinatal findings and molecular cytogenetic characterization of a prenatally detected sacrococcygeal teratoma associated with mosaic r(21). This is the first report of mosaic r(21) presenting with a fetal sacrococcygeal teratoma. We discuss cytogenetic abnormalities associated with fetal sacrococcygeal teratomas.

Uniparental disomy (UPD) is an uncommon chromosome condition, but UPD involving chromosome 21 is rarely reported. We reported here a case who had first trimester screening test for Down syndrome, chorionic villus sampling for fetal karyotyping, quantitative fluorescence polymerase chain reaction (QF-PCR), as well as non-invasive prenatal testing (NIPT) by ...

Pierre Robin sequence (PRS) is a malformation pattern characterized by the core triad of retrognathia, glossoptosis, and cleft palate that causes difficulty in glossopharyngeal-laryngeal-vagal functions. The etiology of PRS remains largely unknown; previous reports have suggested that it is caused by intrauterine constriction or external conditions such as oligohydramnios, breech ...

Microduplications of 22q11.2 have been recently characterized as a new genomic duplication syndrome showing an extremely variable phenotype ranging from normal or mild learning disability to multiple congenital defects and sharing some overlapping features with DiGeorge/Velocardiofacial syndrome (DGS/VCFS). We report on the prenatal diagnosis of a 22q11.2 microduplication in a ...

The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis ...

Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been ...

OBJECTIVE: Studies showing the efficacy and accuracy of chromosomal microarray analysis (CMA) in prenatal diagnosis may position it as a first-tier prenatal test. This study seeks to characterize the practices and attitudes of North American prenatal genetic counselors regarding CMA. METHOD: Genetic counselors (N = 196) in Canada and the USA responded ...

OBJECTIVES: To determine whether there is an association between ultrasonographically assessed hyper- or hypocoiling of the umbilical cord and the presence of Down syndrome (trisomy 21). Furthermore, to provide reference values for the antenatal umbilical coiling index (aUCI) at a gestational age of 16-21 weeks and to determine whether these ...

Miscarriage is the most common adverse outcome in Maternal-Fetal Medicine and has long term psychological impact. Discrepancies in diagnosis and treatment have prompted RCOG and NICE to extend miscarriage diagnostic criteria and ascertain diagnosis through a second opinion and/or a repeat scan. Clinicians should base management on expectant management as ...

Array-CGH or Chromosomal Microarray Analysis (CMA) is increasingly used in prenatal diagnosis throughout the world. However, routine practices are very different among centers and countries, regarding CMA indications, design and resolution of microarrays, notification and interpretation of Copy Number Alterations (CNA). We present our data and experience from our Fetal ...

Partial duplication of 11q is related to several malformations like growth retardation, intellectual disability, hypoplasia of corpus callosum, short nose, palate defects, cardiac, urinary tract abnormalities and neural tube defects. We have studied the clinical and molecular characteristics of a patient with severe intellectual disabilities, dysmorphic features, congenital inguinal hernia ...

Pre-eclampsia is a common vascular disorder of pregnancy. It originates in the placenta and targets the maternal endothelium. According to epidemiological research, >50% of the liability to this disorder can be accounted for by genetic factors. Both maternal and fetal genes contribute to the risk, but especially the fetal genetic ...

BACKGROUND: Although the majority of congenital heart defects (CHDs) occur in isolation, a significant number occur with noncardiac anomalies. This study determined the proportion of noncardiac anomalies among CHD cases in Alberta. METHODS: Records of infants and children born in Alberta between January 1, 1995, to December 31, 2002, were ...

Hybrid zones provide excellent opportunities to study processes and mechanisms underlying reproductive isolation and speciation. Here we investigated sex-specific clines of molecular markers in hybrid zones of morphologically cryptic yet genetically highly-diverged evolutionary lineages of the European common vole (Microtus arvalis). We analyzed the position and width of four secondary ...

The 1997 discovery of free fetal DNA in maternal plasma launched clinical researchers' efforts to establish a reliable method for non-invasive prenatal testing for fetal genetic conditions. Various methods, including, but not limited to, massively parallel sequencing (MPS) and selective analysis of cell-free fetal DNA in maternal plasma, have recently ...

Chromosomal microarray analysis (CMA) has emerged as a powerful new tool to identify genomic abnormalities associated with a wide range of developmental disabilities including congenital malformations, cognitive impairment, and behavioral abnormalities. CMA includes array comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays, both of which are useful for ...

The purpose of this study was to determine the deep sequencing and analytic conditions needed to detect fetal subchromosome abnormalities across the genome from a maternal blood sample. Cell-free (cf) DNA was isolated from the plasma of 11 pregnant women carrying fetuses with subchromosomal duplications and deletions, translocations, mosaicism, and ...

We reported a 2-year-old boy with developmental delay, mild mental retardation, and severe craniofacial malformation, including facial asymmetry with hypoplasia of the left zygoma, maxilla, and mandible, and left anophthalmia and anotia. A genome-wide screen revealed a 1.38Mb duplication on chromosome 1q31.1, which was absent in his parents and 27 ...

Caudal appendage is a rare dysmorphic feature of which etiologic mechanisms are not well understood. Here we report monozygotic (MZ) twin brothers who are discordant for the caudal appendage and multiple congenital anomalies. Twins were the product of a 33 weeks of gestation, monochorionic-diamniotic pregnancy. On admission the proband had ...

Recent epidemiological studies suggest that the maternal genome is an important contributor to spontaneous preterm delivery (PTD). There is also a significant excess of males among preterm born infants, which may imply an X-linked mode of inheritance for a subset of cases. To explore this, we examined the effect of ...

Individuals with terminal and interstitial deletions of chromosome 1p36 have a spectrum of defects that includes eye anomalies, postnatal growth deficiency, structural brain anomalies, seizures, cognitive impairment, delayed motor development, behavior problems, hearing loss, cardiovascular malformations, cardiomyopathy, and renal anomalies. The proximal 1p36 genes that contribute to these defects have ...

A partial duplication of the distal long arm of chromosome 5 (5q35-->qter) is known to be associated with a distinct phenotype referred to as Hunter-McAlpine syndrome. Clinical spectrum of this disorder mainly consists of mental retardation, microcephaly, short stature, skeletal anomalies, and craniofacial dysmorphism featuring flat facies, micrognathia, large, low-set ...

Embryonic development in mammals has evolved a platform for genomic conflict between mothers and embryos and, by extension, between maternal and paternal genomes. The evolutionary interests of the mother and embryo may be maximized through the promotion of sex-chromosome genes and imprinted alleles, resulting in the rapid evolution of postzygotic ...

OBJECTIVES: To assess the frequency of karyotype abnormalities and chromosome 22q11.2 deletion syndrome (22q11.2 DS) among fetuses with cardiac ultrasound findings; and to evaluate the clinical value of chromosomal microarray-based analysis (CMA) for the study of such pregnancies. METHODS: Firstly, retrospective analysis of karyotype abnormalities and 22q11.2 DS cases diagnosed ...

Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Samples from women undergoing prenatal diagnosis at ...

In this study, we aimed to explore the utility of chromosomal microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order to assess whether CMA improves the detection rate of prenatal chromosomal aberrations. ...

Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous syndrome which is characterized by severe intrauterine and postnatal growth retardation, and typical characteristic facial dysmorphisms. It has been associated with maternal uniparental disomy (UPD) for chromosome 7 and hypomethylation of imprinting control region 1 (IGF2/H19) in 11p15. UPD refers to ...

We report a child with segmental maternal uniparental isodisomy of chromosome 6, involving most of the long arm distal to 6q16, detected by SNP microarray. Clinical features include prenatal growth restriction, global developmental delay, and severe gastro-esophageal reflux disease. Maternal uniparental disomy (UPD) of chromosome 6 has previously been reported ...

Split-hand/split-foot malformation (SHFM1) has been reported to be caused by deletions, duplications or rearrangements involving the 7q21.3 region harboring DSS1, DLX5, and DLX6. We report on a female patient with unilateral syndactyly of the third and fourth fingers of the right hand and overgrowth and lateral deviation of the right ...

Abstract In fetal autopsies coronal clefts - a radiolucent band running through at least one vertebral body, visualized in the lateral spinal radiograph and discussed as a physiological variation of the fetal vertebral ossification pattern - are often found in fetuses with trisomies. Published studies are missing concerning the question ...

OBJECTIVE: Down syndrome (DS) has major resource implications especially in developing countries being third most important cause of mental handicap. Maternal serum screening for chromosomal aneuploidies and neural tube defects (NTDs) is practiced worldwide in many countries and has been integrated into mainstream health care, while it is gradually gaining ...

Abstract OBJECTIVE: Prenatal cytogenetic diagnostic methods for the diagnosis of fetal chromosomal anomalies have been used reliably over the last 40 years. Advanced maternal age has become a basic indication for amniocentesis. METHODS: We examined the results of the chromosome analyses of 3485 women that had amniocentesis for any reason ...

a fetus with a ring chromosome 20 is presented. at 16 weeks' gestation, ultrasound examination evidenced no apparent structural malformation. Amniocentesis was performed for maternal anxiety. chromosome analysis identified a ring chromosome 20 and array-CGH demonstrated that the ring including micro-deletion of the short arm in 20p13, that was extended ...

Background: Birth defects are very common, affecting two to three infants in every 100 births, and often represent a diagnostic and management challenge. The birth of a child with multiple malformations is the beginning of a complex diagnostic process, where the primary purpose is to determine a precise nosological definition. ...

We report on a boy presenting submucous cleft palate, hydronephrosis, ventriculoseptal defect, aniridia, and developmental delay. Additional material on 11p13 was cytogenetically visible and array analyses identified a duplicated segment on 15q25-26 chromosome region; further, array analyses revealed a small deletion (49 kb) at 11p13 region involving the ELP4 gene and ...

We report on a 14-year-old girl with growth deficiency, microcephaly, intellectual disability, distinctive dysmorphic features (bulbous nose with wide nasal base, hypotelorism, deeply set eyes, protruding cupped ears, and thick lower lip), cataract, pigmentary retinopathy, hypoplastic thorax, kyphoscoliosis, and unusual skeletal changes but without chromosomal imbalances detected by array-CGH who ...

OBJECTIVE: This study aimed at presenting prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 8 by fluorescence in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR), and array comparative genomic hybridization (aCGH) on uncultured amniocytes. MATERIALS, METHODS, AND RESULTS: A 32-year-old ...

OBJECTIVE: The purpose of this case report is to present prenatal diagnosis and molecular cytogenetic characterization of pure partial monosomy 3p (3p25.3 → pter) by array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) on uncultured amniocytes. CASE REPORT: A 35-year-old, gravida 2, para 0, woman underwent amniocentesis at ...

A case of neonatal diagnosis of 49,XXXXY syndrome is presented. Clinical identification was prompted by a bilateral thickening of the radioulnar joints and X-ray imaging disclosing almost complete radioulnar synostosis. Conventional karyotyping was initiated and revealed a karyotype of 49,XXXXY. Previously reported neonatal symptoms such as low birth weight, muscular ...

Background: Congenital heart defects are the most common group of major birth anomalies and one of the leading causes of infant deaths. Mendelian and chromosomal syndromes account for about 20% of congenital heart defects and in some cases are associated with other malformations, intellectual disability, and/or dysmorphic features. The remarkable ...

The term 'genomic imprinting' refers to selective repression of transcription from distinct chromosomal regions determined by their maternal or paternal inheritance. There are two potentially important aspects of imprinting that may manifest in individuals with X monosomy, or Turner syndrome (TS). Given that men are monosomic for Xm while women ...

Little is known about the behavior of interleukin 15 (IL-15) and 18 (IL-18) in the amniotic fluid in the second trimester of gestations complicated by chromosomal defects in the fetus. Likewise, it has not yet been established whether a fetus with chromosome abnormalities creates its immunity mechanisms in the same ...