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Indian Journal of Clinical Biochemistry... Jan 2013The first trimester screening programme offers a noninvasive option for the early detection of aneuploidy pregnancies. This screening is done by a combination of two... (Review)
Review
The first trimester screening programme offers a noninvasive option for the early detection of aneuploidy pregnancies. This screening is done by a combination of two biochemical markers i.e. serum free β-human chorionic gonadotrophin (free β-hCG) and pregnancy associated plasma protein A (PAPP-A), maternal age and fetal nuchal translucency (NT) thickness at 11 + 0-13 + 6 weeks of gestation. A beneficial consequence of screening is the early diagnosis or trisomies 21, 18 and 13. At 11 + 0-13 + 6 weeks, the relative prevalence of trisomies 18 and 13 to trisomy 21 are found to be one to three and one to seven, respectively. All three trisomies are associated with increased maternal age, increased fetal NT and decreased PAPP-A, but in trisomy 21 serum free β-hCG is increased whereas in trisomies 18 and 13 free β-hCG is decreased.
PubMed: 24381414
DOI: 10.1007/s12291-012-0269-9 -
Chromosome Research : An International... Aug 2023Mistakes in chromosome segregation leading to aneuploidy are the primary cause of miscarriages in humans. Excluding sex chromosomes, viable aneuploidies in humans... (Review)
Review
Mistakes in chromosome segregation leading to aneuploidy are the primary cause of miscarriages in humans. Excluding sex chromosomes, viable aneuploidies in humans include trisomies of chromosomes 21, 18, or 13, which cause Down, Edwards, or Patau syndromes, respectively. While individuals with trisomy 18 or 13 die soon after birth, people with Down syndrome live to adulthood but have intellectual disabilities and are prone to multiple diseases. At the cellular level, mistakes in the segregation of a single chromosome leading to a cell losing a chromosome are lethal. In contrast, the cell that gains a chromosome can survive. Several studies support the hypothesis that gaining an extra copy of a chromosome causes gene-specific phenotypes and phenotypes independent of the identity of the genes encoded within that chromosome. The latter, referred to as aneuploidy-associated phenotypes, are the focus of this review. Among the conserved aneuploidy-associated phenotypes observed in yeast and human cells are lower viability, increased gene expression, increased protein synthesis and turnover, abnormal nuclear morphology, and altered metabolism. Notably, abnormal nuclear morphology of aneuploid cells is associated with increased metabolic demand for de novo synthesis of sphingolipids. These findings reveal important insights into the possible pathological role of aneuploidy in Down syndrome. Despite the adverse effects on cell physiology, aneuploidy is a hallmark of cancer cells. Understanding how aneuploidy affects cell physiology can reveal insights into the selective pressure that aneuploid cancer cells must overcome to support unlimited proliferation.
Topics: Humans; Down Syndrome; Sex Chromosomes; Aneuploidy; Trisomy; Chromosome Segregation
PubMed: 37620607
DOI: 10.1007/s10577-023-09732-w -
Cureus Oct 2022The cell-free fetal DNA (cffDNA) analysis for screening fetal genetic anomalies has increased dramatically since its commercialization in 2011 worldwide. In the early... (Review)
Review
The cell-free fetal DNA (cffDNA) analysis for screening fetal genetic anomalies has increased dramatically since its commercialization in 2011 worldwide. In the early weeks of pregnancy, it offers a hassle-free, non-invasive procedure of antenatal screening. It guides and protects mothers from undergoing unwanted risk-laden invasive prenatal testing. cffDNA testing is accurate at detecting the abnormal fetus chromosome among a large pool population. Patau syndrome, Edward syndrome, and Down syndrome are currently being accurately screened by this method. Due to their sensitivity and specificity, they now have become the screening method of choice, approaching almost 100% in various studies with a large sample pool. The latest procedures to analyze cffDNA, like the new digital droplet polymerase chain reaction (ddPCR) and sophisticated next-generation sequencing (NGS), have increased detection rates with decreased analyzing time. The latest techniques make it possible to screen large numbers of the population with faster report generation. Screening for Rh incompatibility and its timely prevention is now more accessible and more accurate with the help of cffDNA analysis. The problem arises when we deviate from the primary disease and start testing for anomalies not intended to be screened by cffDNA in the first place. Fetal sex chromosome aneuploidy screening by cffDNA is one area where the test gives mixed results either due to differences in machinery, laboratory parameters, or human error. Other rare occurrences like trisomes, such as trisomy 7, trisomy 16, trisomy 22, and a few microdeletion syndromes are also being screened but with less accuracy. Like every technology, cffDNA analysis is not entirely free of criticism. Its high testing cost, potential to accurately prognosticate the gender of the developing fetus and absence of standard testing practices will become an issue as the test becomes routine worldwide.
PubMed: 36381888
DOI: 10.7759/cureus.29965 -
SpringerPlus 2016Kidney diseases are becoming a major cause of global burden with high mortality and morbidity. The origins of most kidney diseases are known, but for some the exact... (Review)
Review
Kidney diseases are becoming a major cause of global burden with high mortality and morbidity. The origins of most kidney diseases are known, but for some the exact aetiology is not yet understood. Dermatoglyphics is the scientific study of epidermal ridge patterns and it has been used as a non-invasive diagnostic tool to detect or predict different medical conditions that have foetal origin. However, there have been a limited number of studies that have evaluated a dermatoglyphic relationship in different kidney diseases. The aim of this review was to systematically identify, review and appraise available literature that evaluated an association of different dermatoglyphic variables with kidney diseases. This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The PubMed(®) (Medline), POPLINE, Cochrane Library and Trip Database and grey literature sources such as OpenGrey, Google Scholar, and Google were searched to earliest date to 17 April 2014. Of the 36 relevant publications, 15 were included in the review. Of these studies, there are five case reports, seven case series and three comparative studies. Possible association of dermatoglyphics with Wilms tumor (WT) had been evaluated in two comparative studies and one case series that found fewer whorls and a lower mean total ridge count (TRC). Another study evaluated adult polycystic kidney disease (APCD) type III that revealed lower TRC means in all cases. All other case series and case reports describe dermatoglyphics in various kidney disease such as acro-renal-ocular syndrome, potter syndrome, kabuki makeup syndrome, neurofaciodigitorenal syndrome, syndactyly type V, ring chromosome 13 syndrome, trisomy 13 syndrome and sirenomelia. It is evident that whorl pattern frequency and TRC have been used widely to investigate the uncertainty related to the origin of several kidney diseases such as WT and APCD type III. However, small sample sizes, possibly methodological issues, and discrepancy in the make up between cases and control groups limits interpretation of any significant findings. Future studies with proper protocol, adequate cases, and control groups may provide stronger evidence to resolve uncertainty related to the aetiology of kidney diseases.
PubMed: 27066327
DOI: 10.1186/s40064-016-1783-7 -
International Journal of Molecular... Nov 2023Trisomy is the presence of one extra copy of an entire chromosome or its part in a cell nucleus. In humans, autosomal trisomies are associated with severe developmental...
Trisomy is the presence of one extra copy of an entire chromosome or its part in a cell nucleus. In humans, autosomal trisomies are associated with severe developmental abnormalities leading to embryonic lethality, miscarriage or pronounced deviations of various organs and systems at birth. Trisomies are characterized by alterations in gene expression level, not exclusively on the trisomic chromosome, but throughout the genome. Here, we applied the high-throughput chromosome conformation capture technique (Hi-C) to study chromatin 3D structure in human chorion cells carrying either additional chromosome 13 (Patau syndrome) or chromosome 16 and in cultured fibroblasts with extra chromosome 18 (Edwards syndrome). The presence of extra chromosomes results in systematic changes of contact frequencies between small and large chromosomes. Analyzing the behavior of individual chromosomes, we found that a limited number of chromosomes change their contact patterns stochastically in trisomic cells and that it could be associated with lamina-associated domains (LAD) and gene content. For trisomy 13 and 18, but not for trisomy 16, the proportion of compacted loci on a chromosome is correlated with LAD content. We also found that regions of the genome that become more compact in trisomic cells are enriched in housekeeping genes, indicating a possible decrease in chromatin accessibility and transcription level of these genes. These results provide a framework for understanding the mechanisms of pan-genome transcription dysregulation in trisomies in the context of chromatin spatial organization.
Topics: Infant, Newborn; Humans; Trisomy; Cell Nucleus; Chromatin; Genetic Testing; Trisomy 13 Syndrome
PubMed: 38003233
DOI: 10.3390/ijms242216044 -
Annals of Medicine and Surgery (2012) Aug 2022and background: Patau syndrome or trisomy 13 is a clinically severe condition; 85 percent of patients die before reaching the age of one year, and the majority of...
INTRODUCTION
and background: Patau syndrome or trisomy 13 is a clinically severe condition; 85 percent of patients die before reaching the age of one year, and the majority of children die before reaching the age of six months.
CASE PRESENTATION
This report discusses a case of a male infant, two days old diagnosed with Patau syndrome. After birth, his APGAR score was satisfactory. The initial clinical examination revealed cleft palate, cleft lip, and congenital clubfoot. A pansystolic murmur was heard at the left sternal border. The patient was managed according and was referred to a surgeon for pulmonary binding, PDA ligation, VSD closure, and repair of ASA with disbanding of the pulmonary artery.
CLINICAL DISCUSSION
Studies have reported that patients with Patau syndrome present with cleft lip and palate, congenital heart defects, omphalocele, and holoprosencephaly. we also discovered dysmorphic characteristics such as the cleft palate and cleft lip, as well as serious congenital cardiac abnormalities. In addition, up to 80% of patients have been documented to have cardiac abnormalities, with patent ductus arteriosus, atrial septal defect, and ventricular septal defect.
CONCLUSION
Patau syndrome is the third most common trisomy found in infants. The clinical manifestation of Patau syndrome includes cleft palate, cleft lip, limb impairments, and congenital heart problems. Despite the fact that early diagnosis and management prognosis is poor for patients suffering from Patau syndrome. Genetic counseling may be beneficial not just for increasing awareness of the diagnosis and its implications.
PubMed: 36045789
DOI: 10.1016/j.amsu.2022.104100 -
The Journal of International Advanced... Nov 2022This study aimed to present the first cochlear implant surgery performed on a patient with Patau syndrome. In the auditory brainstem Response test performed on the 37th...
This study aimed to present the first cochlear implant surgery performed on a patient with Patau syndrome. In the auditory brainstem Response test performed on the 37th month, I-III-V waves at 100 dB were not obtained in the right ear, while I-III-V waves at 90 dB were obtained in the left ear. In the free-field audiometry test done in the first year, the threshold value of cochlear implantation was found to be 45 dB. While the Meaningful Auditory Integration Scale test result was 35/40, the Meaningful Use of Speech Scale test result was 13/40. The cochlear implantation was observed and found that hearing results are good and had a positive effect on the quality of life.
Topics: Child; Humans; Cochlear Implantation; Quality of Life; Trisomy 13 Syndrome; Cochlear Implants; Evoked Potentials, Auditory, Brain Stem; Speech Perception
PubMed: 36349678
DOI: 10.5152/iao.2022.20074 -
Revista Paulista de Pediatria : Orgao... 2023To describe the newborn population with Patau (T13) and Edwards Syndrome (T18) with congenital heart diseases that stayed in the Intensive Care Unit (ICU) of a...
OBJECTIVE
To describe the newborn population with Patau (T13) and Edwards Syndrome (T18) with congenital heart diseases that stayed in the Intensive Care Unit (ICU) of a quaternary care hospital complex, regarding surgical and non-surgical medical procedures, palliative care, and outcomes.
METHODS
Descriptive case series conducted from January/2014 to December/2018 through analysis of records of patients with positive karyotype for T13 or T18 who stayed in the ICU of a quaternary hospital. Descriptive statistics analysis was applied.
RESULTS
33 records of eligible patients were identified: 27 with T18 (82%), and 6 T13 (18%); 64% female and 36% male. Eight were preterm infants with gestational age between 30-36 weeks (24%), and only 4 among the 33 infants had a birth weight >2500 g (12%). Four patients underwent heart surgery and one of them died. Intrahospital mortality was 83% for T13, and 59% for T18. The majority had other malformations and underwent other surgical procedures. Palliative care was offered to 54% of the patients. The median hospitalization time for T18 and T13 was 29 days (range: 2-304) and 25 days (13-58), respectively.
CONCLUSIONS
Patients with T13 and T18 have high morbidity and mortality, and long hospital and ICU stays. Multicentric studies are needed to allow the analysis of important aspects for creating protocols that, seeking therapeutic proportionality, may bring better quality of life for patients and their families.
Topics: Infant; Humans; Male; Infant, Newborn; Female; Trisomy 18 Syndrome; Chromosome Disorders; Trisomy 13 Syndrome; Palliative Care; Quality of Life; Infant, Premature; Hospitals; Trisomy; Retrospective Studies
PubMed: 38088680
DOI: 10.1590/1984-0462/2024/42/2023053 -
Prenatal Diagnosis Dec 2022To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories.
Positive predictive values and outcomes for uninformative cell-free DNA tests: An Italian multicentric Cytogenetic and cytogenomic Audit of diagnOstic testing (ICARO study).
OBJECTIVES
To establish the positive predictive values (PPV) of cfDNA testing based on data from a nationwide survey of independent clinical cytogenetics laboratories.
METHODS
Prenatal diagnostic test results obtained by Italian laboratories between 2013 and March 2020 were compiled for women with positive non-invasive prenatal tests (NIPT), without an NIPT result, and cases where there was sex discordancy between the NIPT and ultrasound. PPV and other summary data were reviewed.
RESULTS
Diagnostic test results were collected for 1327 women with a positive NIPT. The highest PPVs were for Trisomy (T) 21 (624/671, 93%) and XYY (26/27, 96.3%), while rare autosomal trisomies (9/47, 19.1%) and recurrent microdeletions (8/55, 14.5%) had the lowest PPVs. PPVs for T21, T18, and T13 were significantly higher when diagnostic confirmation was carried out on chorionic villi (97.5%) compared to amniotic fluid (89.5%) (p < 0.001). In 19/139 (13.9%), of no result cases, a cytogenetic abnormality was detected. Follow-up genetic testing provided explanations for 3/6 cases with a fetal sex discordancy between NIPT and ultrasound.
CONCLUSIONS
NIPT PPVs differ across the conditions screened and the tissues studied in diagnostic testing. This variability, issues associated with fetal sex discordancy, and no results, illustrate the importance of pre- and post-test counselling.
Topics: Female; Humans; Pregnancy; Cell-Free Nucleic Acids; Cytogenetic Analysis; Predictive Value of Tests; Prenatal Diagnosis; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome; Italy
PubMed: 36403097
DOI: 10.1002/pd.6271 -
International Journal of Clinical and... 2015The study aimed to validate the efficacy of detection of fetal cell-free DNA in maternal plasma of trisomy 21, 18 and 13 in a clinical setting.
OBJECTIVE
The study aimed to validate the efficacy of detection of fetal cell-free DNA in maternal plasma of trisomy 21, 18 and 13 in a clinical setting.
METHODS
A total of 2340 women at high risk for Down syndrome based on maternal age, prenatal history or a positive sesum or sonographic screening test were offered prenatal noninvasive aneuploidy test. According to the prenatal noninvasive aneuploidy test, the pregnant women at high risk were offered amniocentesis karyotype analysis and the pregnant at low risk were followed up to make sure the newborn outcome.
RESULTS
The prenatal noninvasive aneuploidy test was positive for trisomy 21 in 17 cases, for trisomy 18 in 6 cases and for trisomy 13 in 1 case, which of all were confirmed by karyotype analysis. Newborns of low risk gestational woman detected by prenatal noninvasive aneuploidy for trisomy 21, 18, 13 were followed up and no one was found with trisomy.
CONCLUSIONS
The prenatal noninvasive aneuploidy test is highly accurate for detection of trisomy 21, 18 and 13, which can be considered as a practical alternative for traditional invasive diagnostic procedures.
PubMed: 26309618
DOI: No ID Found