Numerical Chromosomal Abnormalities Research Articles

8.3 GENETIC CONDITIONS ASSOCIATED WITH INTELLECTUAL DEVELOPMENTAL DISORDERS

Research on the genetic architecture of intellectual and developmental disorders have revealed a significant contribution of numerical and structural chromosomal abnormalities, rare point mutations, and trinucleotide repeat expansions. Significant advances in technology to identify these mutations as well as the significant reduction in the time and cost required to perform these tests have led to a rapid change in the recommendations regarding genetic testing. The proper genetic workup, when conducted, can help identify these genetic conditions that, if not for their presence, may not have led to the individual manifesting intellectual developmental disorder (IDD). The current recommended genetic evaluation for children with suspected IDD will be reviewed. Newer genetic testing methods will also be presented along with their diagnostic yields. Common genetic syndromes that the child and adolescent psychiatrist may well encounter will be presented along with their common mental health manifestations as well as common medical comorbidities. Psychopharmacological considerations given these comorbidities will be discussed. 1) Increased genetic testing and advances in genetic testing methods have led to an increase in the number of individuals with IDD diagnosed with genetic syndromes. 2) Technology is advancing rapidly in this field and may rapidly become the diagnostic of choice in the near future. 3) The genetic diagnosis of these individuals, in some cases, leads to better prognostication of treatment response to pharmacotherapies, and psychiatrists should be aware of these results. The fraction of children with IDD with known genetic findings is high enough that child and adolescent psychiatrists are well served to be familiar with the more common genetic syndromes.

Analysis of Genomic Copy Number Variation in Miscarriages During Early and Middle Pregnancy.

The purpose of this study was to explore the copy number variations (CNVs) associated with miscarriage during early and middle pregnancy and provide useful genetic guidance for pregnancy and prenatal diagnosis. A total of 505 fetal specimens were collected and CNV sequencing (CNV-seq) analysis was performed to determine the types and clinical significance of CNVs, and relevant medical records were collected. The chromosomal abnormality rate was 54.3% (274/505), among which the numerical chromosomal abnormality rate was 40.0% (202/505) and structural chromosomal abnormality rate was 14.3% (72/505). Chromosomal monosomy mainly occurred on sex chromosomes, and chromosomal trisomy mainly occurred on chromosomes 16, 22, 21, 15, 13, and 9. The incidence of numerical chromosomal abnormalities in ≥35 year-old age pregnant women was significantly higher than <35 year-old age group. The highest incidence of pathogenic CNV (pCNV) was found in fetuses at ≤6 weeks of pregnancy (5.26%), and the incidence of variants of unknown significance (VOUS) CNVs decreased gradually with the increase of gestational age. The rate of chromosomal abnormalities of fetuses in early pregnancy (59.5%) was higher than that of fetuses in middle pregnancy (27.2%) (p < 0.001). There were 168 genes in VOUS + pCNV regions. 41 functions and 12 pathways (p < 0.05) were enriched of these genes by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Some meaningful genetic etiology information such as genes and pathways has been obtained, it may provide useful genetic guidance for pregnancy and prenatal diagnosis.

Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number.

Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum—in the form of aluminum chloride (AlCl3) and at concentrations in the range of those measured in human tissues—incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis.

Copy number variation characterization and possible candidate genes in miscarriage and stillbirth by next-generation sequencing analysis.

BackgroundThe present study aimed to explore the etiological relationship between miscarriage and stillbirth and copy number variations (CNVs), as well as provide useful genetic guidance for high‐risk pregnancy.MethodsIn total, 659 fetal samples were recruited and subjected to DNA extraction and CNV sequencing (CNV‐seq), relevant medical records were collected.ResultsThere were 322 cases (48.86%) with chromosomal abnormalities, including 230 with numerical abnormalities and 92 with structural abnormalities. Chromosomal monosomy variations mainly occurred on sex chromosomes and trisomy variations mainly occurred on chromosomes 16, 22, 21, 18, 13 and 15. In total, 41 pathogenic CNVs (23 microdeletions and 18 microduplications) were detected in 27 fetal tissues. The rates of numerical chromosomal abnormalities were 29.30% (109/372), 32.39% (57/176) and 57.66% (64/111) in < 30‐year‐old, 30–34‐year‐old and ≥ 35‐year‐old age pregnant women, respectively, and increased with an increasing age (p < 0.001). There was statistically significant difference (χ2 = 7.595, p = 0.022) in the rates of structural chromosomal abnormalities in these groups (13.71%, 18.75% and 7.21%, respectively). The rates of numerical chromosomal abnormalities were 45.44% (219/482), 7.80% (11/141) and 0% (0/36) in the ≤ 13 gestational weeks, 14–27 weeks and ≥ 28 weeks groups, respectively, and decreased with respect to the increasing gestational age of the fetuses (p < 0.001).ConclusionsThe present study has obtained useful and accurate genetic etiology information that will provide useful genetic guidance for high‐risk pregnancies.

Efficiency of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies

Objective: This study was designed to investigate the efficiency of noninvasive prenatal testing (NIPT) for screening fetal sex chromosome aneuploidies (SCAs) through sequencing of cell-free DNA in maternal plasma. Methods: This is a retrospective study on the positive NIPT results for SCAs collected from our hospital between January 2012 and December 2018. Samples with positive NIPT results for SCAs were then confirmed by prenatal or postnatal karyotyping analysis. Results: After cytogenetic analysis, abnormal karyotypes were confirmed in 104 cases and the overall positive predictive value (PPV) of NIPT for SCAs was 43.40% (102/235). The most frequently detected karyotypes included 47,XXY (n = 42), 47,XXX (n = 20), 47,XYY (n = 16), and 45,X (n = 2). Meanwhile, 10 cases were confirmed with mosaic karyotype 45,X/46,XX and 14 cases with numerical or structural chromosome abnormalities, including a double trisomy 48,XXX,+18. Cytogenetic results from the other 131 cases showed normal XX or XY, which were discordant with NIPT results. Upon analysis of parental karyotypes, 29 (12.34%) showed false positivity in NIPT results that were caused by maternal sex chromosome abnormalities. Conclusion: NIPT is an effective screening tool for SCA with a PPV of 43.40%. Maternal karyotype abnormalities occurred in 12.34% of the cases with abnormal NIPT. Diagnostic testing of the fetus and the mother are recommended.

English

BACKGROUND Infertility is the inability to become a parent of a child even after one year of intercourse involving male and female partner without any contraceptives. There are many causes for infertility, Y chromosome microdeletion is one among that. Partial or complete deletion of the proximal Yq region, which contains azoospermic factor (AZF) locus, leads to infertility. Along with genetic and biochemical factors the ethno-geographical reasons also play an important role in infertility. The present study was done to identify the association of genetic and hormonal factors in the development of infertility in azoospermic males of southern Kerala. METHODS Retrospectively screened the medical records of 2100 infertile males of the Department of Reproductive Medicine of Sree Avittom Tirunal Hospital, Government Medical College, Thiruvananthapuram for a period from January 2017 to December 2019. Stringent inclusion criterias were taken to select patients for the molecular study and finally 46 were selected. Structural and numerical chromosome abnormalities were detected using karyotyping and microdeletion was identified using polymerase chain reaction. Electro-chemiluminescence immunoassay method was used for the quantification of reproductive hormones. Demographic data of selected patients were collected from the medical records. RESULTS The cytogenetic results showed that among the selected patients, 10.86 % had Klinefelter syndrome and one person had De la Chapelle syndrome. Partial microdeletion in AZFa, b or c regions have been observed in 13.63 % of the patients. The hormonal analysis showed significant change in concentration of reproductive hormones irrespective of genetic defects. Demographic data showed that the majority of participated patients are unskilled/skilled laborers, economically poor and are from urban areas. CONCLUSIONS The study concludes that among the selected patients, 24.49 % have clinically significant chromosomal abnormalities like Klinefelter syndrome, De la Chappelle syndrome and partial microdeletion on the AZF region. Irrespective of genetic defects, significant changes in the concentration of reproductive hormones are also observed. KEYWORDS Azoospermia, Infertility, Karyotyping, Y Chromosome Microdeletion

Cytogenetic analysis of early pregnancy loss after assisted reproduction treatment using intracytoplasmic sperm injection.

To evaluate the incidence of numerical chromosomal abnormalities in the patients with early pregnancy loss (EPL) following in vitro fertilization, and evaluate the role of different confounders of the risk of chromosomal abnormality-related pregnancy loss. A retrospective chart review of all patients from our in vitro fertilization (IVF) center who conceived using assisted reproduction techniques between April 2017 and 2019, who experienced a subsequent early pregnancy loss, and whose abortus materials were successfully karyotyped were included. Of the 243 patients experienced an early loss, the overall rate of chromosomal abnormality was 46.75%. The overall rate of aneuploidy in our patient group was 88.8% (64/72), whereas 6.94% (5/72) of the abnormal karyotypes were polyploid. The most common type of trisomy was Trisomy 16 (20.0%; 11/55) followed by Trisomy 15 (14.5%; 8/55). Univariate and multivariate analyses showed that maternal age (< 35 years) and the total number of retrieved oocytes per cycle (≥ 5) were risk factors for a chromosomal abnormality (< 0.001; < 0.05, respectively). The adjusted OR of karyotypic abnormalities was 0.45 for the antagonist cycle type (p < 0.05), and 0.58 for frozen embryo transfer (p < 0.05). Karyotypic abnormality is one of the main reasons for pregnancy loss following an IVF procedure. Although the pregnancy rates increased as a result of novel technologies, the ratio of EPL is still high. The implementation of preimplantation genetic screening techniques might lower the incidence of EPL due to chromosomal abnormalities, thus decreasing the burden on the physicians and the patients.

Numerical and Structural Chromosomal Abnormalities Associated with Immunodeficiency

Numerical and Structural Chromosomal Abnormalities Associated with Immunodeficiency

Genomic and structural abnormalities of the chromosome set of the fetus, depending on the age of pregnant women

To study the frequency and spectrum of fetal chromosomal abnormalities in pregnant women, depending on age, a cytogenetic study of 2248 biopsies of the chorion and placenta, cord blood lymphocytes and amniocytes was carried out in 2016-2020. The work used the generally accepted methods of direct preparation of chromosome preparation and methods of cell cultivation. The analysis of the preparations was performed based on GTG, CBG staining method and FISH method, using DNA probes for centromeric regions 13, 18, 21 and X, Y chromosomes. Numerical and structural abnormalities of chromosomes were considered according to the ISCN 2013 system. As a result of the study, 272 (12.1%) cases of genomic and structural abnormalities of the fetus chromosomes of the fetus of pregnant women were registered. Genomic abnormalities were 69.1%, and chromosome structural rearrangements - 30.9%. Among genomic disorders, the frequency of the Down syndrome in the karyotype of the fetus was 58.5%. Frequency of occurrence of fetal chromosomal abnormalities varies significantly depending on the age group of pregnant women. The frequency of fetal chromosomal pathology in pregnant women under 20 years old was 4.4%, at the age from 20 to 34 years old - 7.6%, from 35 to 39 years old - 16.3%, from 40 to 44 years old - 19.8% , after 45 years figure increased significantly - up to 29.6%. In older pregnant women, when compared with pregnant women of the reproductive period from 20 to 34 years, when the highest level of pregnancy rate (54.6%) in the population is observed, there is an increase in the frequency of fetal chromosomal pathology by 2.1; 2.6 and 3.9 times, respectively.

Study of the Chromosomal Abnormalities and Associated Complex Karyotypes in Hematological Cancer in the Population of West Bengal: A Prospective Observational Study

AbstractIntroduction Chromosomal instability is an important feature of hematological cancer. The pathogenesis is complex and it involves genetic and epigenetic factors. As a genetic factor, chromosomal instability may play a key role in leukemogenesis. Accumulation of genetic alteration is mainly responsible for numerical and structural chromosomal rearrangement or clonal evaluation. But disease progression is often driven by chromosomal translocation, hyper- or hypodiploidy with structural abnormalities, and complex karyotypes.Objective This research aimed to study the different types of chromosomal abnormalities in clinically suspected hematological cancer patients.Materials and Methods Cytogenetic analysis was performed based on phytohemaglutinin stimulated peripheral blood lymphocyte cultures and bone marrow culture, without mitogen, of the respective patients of West Bengal from March 2016 to February 2018. All clinically suspected hematological cancer patients referred for karyotyping to the institutional genetics department have been included without any biasness of sex and age. Karyotypes were described according to the International System for Cytogenetic Nomenclature (ISCN 2005).Results In the present study, 56 clinically suspected hematological cancer cases were observed and 41 cases of chromosomal rearrangement were found which clearly show chromosomal instability as the main driving force for hematological cancer transformation. Presence of variant Philadelphia chromosomes with classical translocation, mosaic complex karyotypes, variable numerical, and structural chromosomal abnormality, along with severe-to-moderate hypo- and hyperdiploidy, and presence of marker chromosomes were the main findings of this study.Conclusion The result shows that the detection of chromosomal instability was important for preliminary diagnosis, treatment, prognosis, and further management. So the present study provided additional information about chromosomal instability in hematological cancer at Kolkata and adjoining regions.

Maternal germline factors associated with aneuploid pregnancy loss: a systematic review.

Miscarriage describes the spontaneous loss of pregnancy before the threshold of viability; the vast majority occur before 12 weeks of gestation. Miscarriage affects one in four couples and is the most common complication of pregnancy. Chromosomal abnormalities of the embryo are identified in ∼50% of first trimester miscarriages; aneuploidy accounts for 86% of these cases. The majority of trisomic miscarriages are of maternal origin with errors occurring during meiotic division of the oocytes. Chromosome segregation errors in oocytes may be sporadic events secondary to advancing maternal age; however, there is increasing evidence to suggest possible maternal germline contributions to this. The objective of this review was to appraise critically the existing evidence relating to maternal germline factors associated with pregnancy loss secondary to embryo aneuploidy, identify limitations in the current evidence base and establish areas requiring further research. The initial literature search was performed in September 2019 and updated in January 2021 using the electronic databases OVID MEDLINE, EMBASE and the Cochrane Library. No time or language restrictions were applied to the searches and only primary research was included. Participants were women who had suffered pregnancy loss secondary to numerical chromosomal abnormalities of the embryo. Study identification and subsequent data extraction were performed by two authors independently. The Newcastle-Ottawa Scale was used to judge the quality of the included studies. The results were synthesized narratively. The literature search identified 2198 titles once duplicates were removed, of which 21 were eligible for inclusion in this systematic review. They reported on maternal germline factors having variable degrees of association with pregnancy loss of aneuploid origin. The Online Mendelian Inheritance in Man (OMIM) gene ontology database was used as a reference to establish the functional role currently attributed to the genes reported. The majority of the cases reported and included were secondary to the inheritance of maternal structural factors such as Robertsonian translocations, deletions and insertions. Germline factors with a plausible role in aneuploid pregnancy loss of maternal origin included skewed X-inactivation and CGG repeats in the fragile X mental retardation (FMR1) gene. Studies that reported the association of single gene mutations with aneuploid pregnancy loss were conflicting. Single gene mutations with an uncertain or no role in aneuploid pregnancy loss included mutations in synaptonemal complex protein 3 (SYCP3), mitotic polo-like kinase 4 (PLK4) and meiotic stromal antigen 3 (STAG3) spindle integrity variants and 5,10-methylenetetrahydrofolate reductase (MTHFR). Identifying maternal genetic factors associated with an increased risk of aneuploidy will expand our understanding of cell division, non-disjunction and miscarriage secondary to embryo aneuploidy. The candidate germline factors identified may be incorporated in a screening panel for women suffering miscarriage of aneuploidy aetiology to facilitate counselling for subsequent pregnancies.

Retrospective analysis of prenatal invasive diagnostic procedures in a tertiary center

Objective: This study aimed to analyze the indications and outcomes of prenatal invasive diagnostic procedures performed in a single tertiary center.&#x0D; Materials and Methods: The invasive procedure indications and karyotype results of 1666 pregnant women who underwent prenatal invasive procedures between March 2016 and November 2018 were retrospectively analyzed. The indications and results of prenatal invasive diagnostic procedures were recorded.&#x0D; Results: Amniocentesis (AS) was performed to 1060 (63.6%) patients, corion villus sampling (CVS) to 299 (17.9%), and cordocentesis (CS) to 307 (18.4%) patients. Among the prenatal invasive procedure indications, the most frequent indication was abnormal ultrasound (US) findings, with a rate of 48.3% (n= 805). A normal karyotype was detected in 85% (n= 1416) of the cases, and chromosomal abnormality was detected in 12.2% (n= 204) of the cases. Abnormal karyotype results were found in 111 (10.5%) of 1060 patients who underwent AS, 87 (29.1%) of 299 patients who underwent CVS, and 52 (16.9%) of 307 patients who underwent CS. Among the numerical chromosomal abnormalities, trisomy 21 was the most common abnormality with a rate of 46% (94/204), while inversions were the most common abnormality of structural chromosomal abnormalities at 8.8% (18/204).&#x0D; Conclusion: The results of the current study show that AS is the most common prenatal diagnostic invasive procedure. We obtained the highest fetal chromosomal anomaly rate in patients who experienced CVS. Abnormal US findings were the most common prenatal invasive diagnostic procedure indication in our study. Choosing the most appropriate invasive procedure is related to the obstetricians' experience, medical history of the patient, the gestational week at admission, maternal prenatal serum screening test results, and abnormal US findings.

Chromosome Abnormalities and Fertility in Domestic Bovids: A Review.

Simple SummaryIn domestic bovids, numerical autosome abnormalities have been rarely reported, as they present abnormal animal phenotypes quickly eliminated by breeders. However, numerical abnormalities involving sex chromosomes and structural (balanced) chromosome anomalies have been more frequently detected because they are most often not phenotypically visible to breeders. For this reason, these chromosome abnormalities, without a cytogenetic control, escape animal selection, with subsequent deleterious effects on fertility, especially in female carriers.After discovering the Robertsonian translocation rob(1;29) in Swedish red cattle and demonstrating its harmful effect on fertility, the cytogenetics applied to domestic animals have been widely expanded in many laboratories in order to find relationships between chromosome abnormalities and their phenotypic effects on animal production. Numerical abnormalities involving autosomes have been rarely reported, as they present abnormal animal phenotypes quickly eliminated by breeders. In contrast, numerical sex chromosome abnormalities and structural chromosome anomalies have been more frequently detected in domestic bovids because they are often not phenotypically visible to breeders. For this reason, these chromosome abnormalities, without a cytogenetic control, escape selection, with subsequent harmful effects on fertility, especially in female carriers. Chromosome abnormalities can also be easily spread through the offspring, especially when using artificial insemination. The advent of chromosome banding and FISH-mapping techniques with specific molecular markers (or chromosome-painting probes) has led to the development of powerful tools for cytogeneticists in their daily work. With these tools, they can identify the chromosomes involved in abnormalities, even when the banding pattern resolution is low (as has been the case in many published papers, especially in the past). Indeed, clinical cytogenetics remains an essential step in the genetic improvement of livestock.

Uterine Leiomyomas with an Apparently Normal Karyotype Comprise Minor Heteroploid Subpopulations Differently Represented in vivo and in vitro

In the present study, we aimed to check whether uterine leiomyomas (ULs) with an apparently normal karyotype in vitro comprise “hidden” cell subpopulations with numerical chromosome abnormalities (heteroploid cells). A total of 32 ULs obtained from 32 patients were analyzed in the study. Each UL was sampled for in vivo and in vitro cytogenetic studies. Karyotyping was performed on metaphase preparations from the cultured UL samples. A normal karyotype was revealed in 20 out of the 32 ULs, of which 9 were selected for further study based on the good quality of the interphase preparations. Then, using interphase FISH with centromeric DNA probes, we analyzed the copy number of chromosomes 7 and 16 in 1,000 uncultured and 1,000 cultured cells of each selected UL. All of the ULs included both disomic cells representing a predominant subpopulation and heteroploid cells reaching a maximum frequency of 21.6% (mean 9.8%) in vivo and 11.5% (mean 6.1%) in vitro. The spectrum of heteroploid cells was similar in vivo and in vitro and mostly consisted of monosomic and tetrasomic cells. However, their frequencies in the cultured samples differed from those in the uncultured ones: while the monosomic cells decreased in number, the tetrasomic cells became more numerous. The frequency of either monosomic or tetrasomic cells both in vivo and in vitro was not associated with the presence of MED12 exon 2 mutations in the tumors. Our results suggest that ULs with an apparently normal karyotype consist of both karyotypically normal and heteroploid cells, implying that the occurrence of minor cell subpopulations with numerical chromosome abnormalities may be considered a characteristic of UL tumorigenesis. Different frequencies of heteroploid cells in vivo and in vitro suggest their dependence on microenvironmental conditions, thus providing a pathway for regulation of their propagation, which may be important for the UL pathogenesis.

The Prevalence and Type of Congenital Heart Diseases in Cytogenetic and Monogenic Chromosomal Rearrangements

In this study, it was aimed to investigate the pattern of congenital heart diseases in cytogenetic and monogenic chromosomal rearrangements. The pediatric age group patients who had been followed between January 2009 and December 2014 by the Genetic Department because of their syndromic manner were enrolled in the study. A total of 301 patients with clinical features were evaluated for cardiac diseases. Echocardiography and standard karyotype studies were performed in all patients. Statistically significant difference of congenital heart disease prevalence between numerical and structural chromosomal abnormalities was found in terms of appearance (p < 0.001). Congenital heart diseases prevalence was 62.5% in trisomy 21, 91% in trisomy 18, and 100% in trisomy 13. Fourteen percent of Turner syndrome patients and 8% of patients with other sex chromosome abnormalities had congenital heart diseases. VACTERL association and DiGeorge syndrome were accompanied by congenital heart diseases with the same rate of 73%. Congenital heart diseases prevalence was 50% among the Williams syndrome patients and 42.4% among the Noonan syndrome patients. There was dilated cardiomyopathy in a patient who was diagnosed with Alstrom syndrome. The prevalence of congenital heart diseases in derivative chromosomal anomalies was statistically significantly higher than the other chromosomal abnormalities with the rate of 62.5% (p < 0.001). Complex cardiac malformations are seen in patients with autosomal chromosomal aneuploidies rather than in patients with sex chromosomal aneuploidies and single gene mutations. CHD has been found with a higher rate in patients with derivative chromosome abnormalities compared with the other structural chromosome abnormalities like deletion, inversion, and translocation. We believe that the patients who are diagnosed with derivative chromosomal abnormalities as a result of genetic testing should be considered for cardiac malformations.

Роль хромосомных аберраций эмбриона в генезе привычного и спорадического невынашивания беременности

Objective. To compare the frequency and nature of embryo/fetus chromosomal abnormalities (CA) in sporadic and recurrent pregnancy loss. Patients and methods. A retrospective cohort study that included 1000 patients with pregnancy loss at 6–12 weeks of gestation. The first group consisted of 681 patients who had their first sporadic miscarriage. The second group consisted of 319 patients who previously had a miscarriage. Chromosomal microarray analysis (CMA) of abortive material was performed. Results. In the first group, various chromosomal abnormalities in the embryo/fetus were detected in 378 (55.5%) samples, in the second group – in 203 (63.5%). The incidence of CA in patients with a history of miscarriage was higher than in sporadic miscarriage, the differences were statistically reliable (p = 0.015). No significant differences were found in the structure of CA. Autosomal trisomies and numerical abnormalities of sex chromosomes were most frequently detected. Conclusion. Chromosomal abnormalities in the embryo are a significant cause of miscarriage, both sporadic and recurrent. Genetic analysis of abortive material is an important component of the examination for choosing further management tactics for patients. CMA is an effective research method when conducting genetic analysis of conception products. Key words: pregnancy loss, preconception planning, recurrent miscarriage, chromosomal abnormalities, chromosomal microarray analysis

Prevalence of Abnormal Karyotypes among Males with Non-obstructive Azoospermia and Severe Oligozoospermia: A Retrospective Study

Introduction: Chromosomal abnormalities are one of the important causes of male infertility. Numerical and structural chromosomal abnormalities are seen frequently in men with azoospermia and severe oligospermia. Other abnormalities include Y Chromosome Microdeletions (YCMD), Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations affecting the internal ductal system, genes affecting sperm function and other non-specific disorders. Upto 14% of the men with azoospermia and severe oligospermia have karyotypic abnormalities. Aim: To determine the prevalence of abnormal karyotypes among men with azoospermia and severe oligozoospermia (&lt;5 million/mL). Materials and Methods: The present study was a retrospective observational study carried out at the Fertility Clinic, Institute of Maternal and Child Health, Calicut, Kerala, India, on patients who attended the Infertility Department between January 2016 to December 2019. Semen analysis was done on 232 patients with 100 patients of azoospermia and 132 patients of oligozoospermia. Karyotyping was done from the Cytogenetics Unit, Department of Anatomy. The data was entered in MS excel sheet and analysed and results were expressed in percentage. Results: Chromosomal abnormalities were detected in 35 (35%) of 100 azoospermia and 15 (11.3%) of 132 severe oligospermia cases analysed. Klinefelter syndrome was the most common abnormality detected in azoospermia (22/35). A 46XX was found in two cases. Structural abnormalities were detected in three case (46 X, der X, 46XY der Chr 1 and Chr 9 inversion). Small Y was found in three cases. Polymorphic variants were found in five patients (46XY 15pstk+, 46XY 15ps+, 46XY 1qh+, 46XY 9qh+). Small Y was found in one case. In oligozoospermia, autosomal translocations were found in four cases {46XY, t(11;13)(q21;q21.2), 46XY, t(1;9) (p13;p21), 46XY, t(13;15)(q34;q21), 46XY, t(7,14) (q34:q11)}, Derivative (46XY der 15) and Marker chromosome (47XY+mar) in one case each. Klinefelter syndrome was found in two cases and 48XXYY was found in one patient. Polymorphic variants were found in five cases (46XY 21pstk,46XY 15ps+, 46XY 1qh-, 48XY 9qh+). Small Y was found in one case. Conclusion: Sex chromosomal and autosomal abnormalities are found frequently in azoospermia and severe oligospermia and hence, genetic screening and counseling before Intracytoplasmic Sperm Injection (ICSI) is warranted.

Prenatal Markers of Foetal Complications

Prenatal markers are commonly used in practice to screen for some foetal abnormalities. They can be biochemical or ultrasonic markers in addition to the newly used cell free Deoxyribonucleic Acid (DNA) estimation. This review aimed to illustrate the applications of the prenatal screening, and the reliability of these tests in detecting the presence of abnormal chromosomes such as trisomy-21, trisomy-18, and trisomy-13 in addition to neural tube defects. Prenatal markers can also be used in the anticipation of some obstetrical complications depending on levels of these markers in the mother’s circulation. In the developed countries, prenatal screening tests are regularly used during antenatal care period. Neural tube defects, numerical and structural chromosomal abnormalities, in addition to some obstetrical problems are commonly screened for, by using prenatal tests. Maternal education about the importance of performing these tests should be done in order to improve the detection rate of foetal abnormalities and some pregnancy complications.

Evaluation of conventional cytogenetic, molecular cytogenetics and molecular genetics results in hematological malignances

Objective: Hematological malignancies are neoplasms of bone marrow-derived cells. Recent studies show that most of these malignancies contain numerical and structural chromosomal abnormalities. These specific gene-level changes are crucial at diagnosis and prognosis evaluation of these diseases. Our study aims to investigate some of these genetic changes and their effect on the etiology and prognosis of hematological malignancies. Materials and Methods: In this study, 110 patients who were admitted to the Department of Hematology of Süleyman Demirel University Faculty of Medicine with a pre-diagnosis or diagnosis of Hematologic Malignancy were included. Three different analyses applied to the cultured bone marrow tissue samples of seven groups of hematology patients who suffered from Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML), Chronic Lymphoblastic Leukemia (CLL), Myelodysplastic Syndrome (MDS), Chronic Myeloproliferative Disease (CMPD), Malignant Plasma Cell Neoplasm (MPCN) and Lymphoma diseases.Numerical and structural chromosomal changes were examined by cytogenetic chromosome analysis and Fluorescent In Situ Hybridization (FISH) methods and JAK-2 V617F mutation was analyzed by Real-Time PCR (RT-PCR). Results: Some mutations were found important in particular diseases such as t(9;22) mutation for CML, t(15;17) for AML; del(5q) and del(7q) for MDS; del(13q14) and del(17p13) mutations for lymphoma, CLL and MPCN. JAK-2 V617F mutations were found effective on CMPD disease subgroups at rates changing from 43% up to 92% according to the RT-PCR results. Conclusion: As a result of our findings, we think that examining patients with hematologic malignancies in their mutations, in addition to the routinely studied existing genetic analyzes, will contribute to the evaluation of the diagnosis and prognosis of the disease.

DAPI Banding Pattern of Chromosomes in Several Brassicaceae Species

BRASSICACEAE family includes a number of the most important Brassica cultivars such as canola, mustard and cabbage, and Arabidopsis thaliana as plant biology model species. Chromosome banding is the most probable protocol for karyotyping and to distinguish numerical chromosome abnormalities, duplications, inversions or deletions of chromosome parts, or exchanging a part from one to another chromosome as well. The aim of this study is to illustrate the DAPI banding patterns in 16 Brassicaceae species with small chromosome size, and they have different origin, ploidy level (chromosome number varies from 2n= 14 to 2n= 32). These species belong to five tribes (Brassiceae, Sisymbrieae, Lepidieae, Arabideae and Alyssea. The aim of this study is to illustrate the DAPI banding patterns in 16 Brassicaceae species with small chromosome size, and they have different origin and ploidy level (chromosome number varies from 2n= 14 to 2n= 32). In the current study we investigated different genera belong to five tribes of the family in regard to the position of regions as by using DAPI staining. It was excluded that most of plants with small chromosomes have mostly a centromeric bands and the more the chromosome size the more tendency to have interstitial bands.