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OBJECTIVES: Determine the incremental diagnostic yield of prenatal exome sequencing (pES) over chromosome microarray (CMA) or G-banding karyotype in fetuses with central nervous system (CNS) abnormalities. METHODS: Data were collected via electronic searches from January 2010 to April 2022 in MEDLINE, Cochrane, Web of Science and EMBASE. The NHS England prenatal exome cohort was also included. Incremental yield was calculated as a pooled value using a random-effects model. RESULTS: Thirty studies were included (n = 1583 cases). The incremental yield with pES for any CNS anomaly was 32% [95%CI 27%-36%; I2 = 72%]. Subgroup analysis revealed apparent incremental yields in; (a) isolated CNS anomalies; 27% [95%CI 19%-34%; I2 = 74%]; (b) single CNS anomaly; 16% [95% CI 10%-23%; I2 = 41%]; (c) more than one CNS anomaly; 31% [95% Cl 21%-40%; I2 = 56%]; and (d) the anatomical subtype with the most optimal yield was Type 1 malformation of cortical development, related to abnormal cell proliferation or apoptosis, incorporating microcephalies, megalencephalies and dysplasia; 40% (22%-57%; I2 = 68%). The commonest syndromes in isolated cases were Lissencephaly 3 and X-linked hydrocephalus. CONCLUSIONS: Prenatal exome sequencing provides a high incremental diagnostic yield in fetuses with CNS abnormalities with optimal yields in cases with multiple CNS anomalies, particularly those affecting the midline, posterior fossa and cortex.

Lilies are highly regarded for their ornamental appeal and striking flowers, which are of significant importance in horticulture. Understanding the genetic makeup of these plants is crucial for breeding and developing new cultivars. This study presents a comprehensive cytogenetic analysis of 45 S and 5 S rDNA loci in 34 wild Lilium species. To reveal the genetic relationships within the genus, advanced visualization methods, such as heatmaps and 3D network plots, were utilized. The results of this study identified both conserved and divergent genetic features, which offer insights into the evolutionary history and potential genetic compatibility of these species. Notably, the clustering of species based on rDNA locus patterns highlights the need for potential taxonomic re-evaluation and reveals candidates for cross-breeding. This integrated approach emphasizes the importance of combining cytogenetic data with traditional morphological classifications to refine our understanding of the Lilium species. Future research should expand the range of analyzed species, incorporate additional molecular markers to further elucidate genetic relationships, and support the development of resilient and diverse ornamental crops. The findings of this study provide a novel framework for genetic analysis of Lilium, offering valuable insights for both scientific understanding and practical breeding programs. [ABSTRACT FROM AUTHOR]

Objective: This work aimed to investigate the potential correlation between chromosomal polymorphisms and various reproductive abnormalities. Methods: We examined 21,916 patients affected by infertility who sought care at the Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University between January 2018 and December 2022. A total of 2227 individuals identified as chromosomal polymorphism carriers constituted the polymorphism group, and 2245 individuals with normal chromosome karyotypes were randomly selected to form a control group. Clinical manifestations, histories of spontaneous miscarriage, abnormal reproductive developments, fetal abnormalities, and male sperm quality anomalies were statistically compared between these two groups. Results: Of the 21,916 patients analyzed, 2227 displayed chromosomal polymorphism, representing a 10.16% detection rate. Amongst the male patients, 1622 out of 10,827 exhibited polymorphisms (14.98%), whereas 605 out of 11,089 females showed polymorphisms (5.46%). Female carriers in the polymorphism group, showed statistically significant increased rates of spontaneous abortion (29.75% vs. 18.54%), fetal anomalies (1.32% vs. 0.81%), and uterine abnormalities compared with the control group (1.32% vs. 0.81%). Male carriers in the polymorphism group had higher rates of spontaneous abortion in partners (22.87% vs. 10.37%), fetal anomalies (1.97% vs. 0.25%), compromised sperm quality (41.74% vs. 7.18%), testicular underdevelopment (2.28% vs. 0.92%), and hypogonadotropic hypogonadism (0.62% vs. 0.37%) compared with the control group. Conclusion: Chromosomal polymorphisms may have a certain negative effect on reproductive irregularities, including spontaneous abortions, fetal anomalies, and reduced sperm quality in males. Their clinical effects deserve further investigation. [ABSTRACT FROM AUTHOR]

Objective: To explore the genetic diagnosis of fetuses with polyhydramnios using chromosomal microarray analysis (CMA). Methods: A total of 112 cases of the polyhydramnios diagnosed by prenatal ultrasound at Quanzhou Women′s and Children′s Hospital from January 2017 to April 2023 were collected. All of the enrolled subjects underwent chromosomal karyotype and CMA analysis. According to the results of ultrasound, the subjects were divided into three groups, the isolated polyhydramnios group (16 cases), the group of polyhydramnios with ultrasound structural abnormalities (27 cases), and the group of polyhydramnios with abnormal ultrasound soft markers (69 cases). Results: Chromosome karyotype analysis found 4 cases of chromosomal aneuploidy, 1 case of aneuploid chromosomal chimerism, and 1 case of chromosomal structural abnormality chimerism, with an abnormal detection rate of 5.36% (6/112). CMA detected all chromosomal abnormalities, and 4 additional cases of pathogenic or likely pathogenic copy number variants, with an additional detection rate of 3.57% (4/112). In addition, there was no statistical difference in the positive detection rate among three groups (P=0.571). Conclusions: Pregnancy with polyhydramnios may be related to fetal chromosomal abnormalities. The chromosome karyotype analysis combined with CMA technique is beneficial to detect more pathogenic copy number variants. Therefore, the chromosome karyotype analysis combined with CMA detection can be recommended in the genetic etiology analysis and prognosis evaluation of fetuses with polyhydramnios. [ABSTRACT FROM AUTHOR]

We reported a case of fetal lymphedema. The chromosome karyotype analysis of fetus and single nucleotide polymorphism array (SNP array) of the amniotic fluid cells showed no abnormalities in the mid pregnancy. However, the pregnant woman perceived a decrease in fetal movement in the late pregnancy, and ultrasound indicated intrauterine stillbirth. Whole exome sequencing (WES) showed that the fetus carried loss of heterozygosity of CELSR1 gene c.5060-1_ 5069 delGCCATGCCTCA. The WES results also showed that the fetal father also carried the mutation and had a normal phenotype. There is a certain correlation between loss of heterozygosity in the CELSR1 gene and lymphedema, but its clinical phenotype is incomplete penetrance. [ABSTRACT FROM AUTHOR]

We generated and characterized a rhesus macaque induced pluripotent stem cell (iPSC) line using induced reprogramming of fibroblasts isolated from a rhesus macaque fetus. The fibroblasts were expanded and then reprogrammed using non-integrating Sendai virus technology. This line is available as riPSC05. The authenticity of riPSC05 was confirmed through the expression of pluripotent and self-renewal markers, in vitro-directed differentiation towards three germ layers (ectoderm, mesoderm, and endoderm), karyotyping, and STR analysis.

Swyer syndrome is a rare genetic disorder in which gonadal dysgenesis and karyotype 46, XY are observed. In the postnatal and prepubescent period, this disease has no clinical manifestations and is asymptomatic, which makes diagnosis difficult. The first signs of the syndrome appear in puberty in the form of underdevelopment of secondary sexual characteristics. This review presents the criteria based on which such a diagnosis as Swyer syndrome can be made. The main diagnostic methods are highlighted, the possibilities of both surgical treatment of patients and drug treatment due to hormone replacement therapy are considered. Verification of the syndrome contributes to a more thorough examination, which will allow you to determine management tactics and avoid complications from other organs and systems.

Abstract Objective This work aimed to investigate the potential correlation between chromosomal polymorphisms and various reproductive abnormalities. Methods We examined 21,916 patients affected by infertility who sought care at the Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University between January 2018 and December 2022. A total of 2227 individuals identified as chromosomal polymorphism carriers constituted the polymorphism group, and 2245 individuals with normal chromosome karyotypes were randomly selected to form a control group. Clinical manifestations, histories of spontaneous miscarriage, abnormal reproductive developments, fetal abnormalities, and male sperm quality anomalies were statistically compared between these two groups. Results Of the 21,916 patients analyzed, 2227 displayed chromosomal polymorphism, representing a 10.16% detection rate. Amongst the male patients, 1622 out of 10,827 exhibited polymorphisms (14.98%), whereas 605 out of 11,089 females showed polymorphisms (5.46%). Female carriers in the polymorphism group, showed statistically significant increased rates of spontaneous abortion (29.75% vs. 18.54%), fetal anomalies (1.32% vs. 0.81%), and uterine abnormalities compared with the control group (1.32% vs. 0.81%). Male carriers in the polymorphism group had higher rates of spontaneous abortion in partners (22.87% vs. 10.37%), fetal anomalies (1.97% vs. 0.25%), compromised sperm quality (41.74% vs. 7.18%), testicular underdevelopment (2.28% vs. 0.92%), and hypogonadotropic hypogonadism (0.62% vs. 0.37%) compared with the control group. Conclusion Chromosomal polymorphisms may have a certain negative effect on reproductive irregularities, including spontaneous abortions, fetal anomalies, and reduced sperm quality in males. Their clinical effects deserve further investigation.

Abstract Background Posterior fossa malformation (PFM) is a relatively uncommon prenatal brain malformation. Genetic diagnostic approaches, including chromosome karyotyping, copy number variant (CNV) testing, and whole-exome sequencing (WES), have been applied in several cases of fetal structural malformations. However, the clinical value of appropriate genetic diagnostic approaches for different types of PFMs has not been confirmed. Therefore, in this study, we aimed to analyze the value of different combined genetic diagnostic approaches for various types of fetal PFMs. Methods This retrospective study was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital. Fifty-one pregnant women diagnosed with fetal PFMs who underwent genetic testing in our hospital from January 1, 2017 to December 31, 2022 were enrolled; women with an isolated enlarged cisterna magna were excluded. All participants were categorized into two groups according to the presence of other abnormalities: isolated and non-isolated PFMs groups. Different combined approaches, including karyotype analysis, CNV testing, and trio-based WES, were used for genetic analysis. The detection rates of karyotype analysis, CNV testing, and WES were measured in the isolated and non-isolated groups. Results In isolated PFMs, pathogenic/likely pathogenic (P/LP) CNVs were detected in four cases (36.36%, 4/11), whereas G-banding karyotyping and WES showed negative results. In non-isolated PFMs, a sequential genetic approach showed a detection rate of 47.5% (19/40); karyotyping revealed aneuploidies in five cases (16.67%, 5/30), CNV testing showed P/LP CNVs in five cases (16.13%, 5/31), and WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4) in nine cases (40.91%, 9/22). WES showed a detection rate of 83.33% (5/6) in fetuses with Joubert syndrome. Only six patients (five with Blake’s pouch cyst and one with unilateral cerebellar hemisphere dysplasia) survived. Conclusions We recommend CNV testing for fetuses with isolated PFMs. A sequential genetic approach (karyotyping, CNV testing, and WES) may be beneficial in fetuses with non-isolated PFMs. Particularly, we recommend WES as the first-line genetic diagnostic tool for Joubert syndrome.

Objective: Rare coexistence of disease or pathology. Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of the Philadelphia (Ph) chromosome, which results from the fusion of the translocation of the ABL1 gene from chromosome 9 to the BCR gene located in chromosome 22, forming the BCR-ABL gene on chromosome number 22, which accounts for approximately 95% of CML cases. Complex translocation involving other chromosomes can occur. Case Report: We present a rare case of CML with a variant Ph chromosome, in which chromosome 16 was involved with the usual translocation. A 34-year-old woman presented with a history of left upper quadrant pain and excessive sweating, with no hepatosplenomegaly on examination. She was found to have leukocytosis, with elevated neutrophils (34 000/mm3), basophils (1460/mm3), and eosinophils (2650/mm3). Karyotyping showed a translocation (16;22) (q24,q11.2), and FISH analysis showed BCR-ABL fusion as a result of (9,22) translocation, with a third chromosome (chromosome 16) involved and fused with chromosome 22, with a different breakpoint, which has never been reported in the literature, affecting the long arm of chromosome 16. The patient was treated with a first-generation tyrosine kinase inhibitor (imatinib) and achieved a deep molecular remission. The repeated FISH analysis confirmed the disappearance of both translocations (9,22) and (16,22). Conclusions: The impact of the additional chromosomal aberration in CML is widely heterogeneous, and the outcome is dependent on multiple factors. Larger studies are needed to clarify the outcome in CML with variant Ph chromosomes, as most of the available data come from reported cases. [ABSTRACT FROM AUTHOR]

Objective To analyze blood lipid levels in patients with myelodysplastic syndrome (MDS) and further explore the factors associated with abnormal blood lipids. Methods Eighty-eight newly diagnosed MDS patients were selected as the study group, and 100 healthy subjects were selected as the control group. Fasting blood lipid levels, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1) and ApoB were detected before treatment in the study group and the control group. The differences of serum lipid levels in MDS patients with different WHO-MDS classification, modified International Prognostic Score System (IPSS-R) karyotype, risk stratification and TP53 mutation were investigated. The correlation between ApoA1 level and clinical indicators of MDS patients was analyzed, and clinical indicators of different ApoA1 level groups were compared. Results The levels of TC, HDL-C, LDL-C, ApoA1 and ApoB were significantly lower in the study group than those in the control group (P＜0.01). There were no significant differences in TG, TC, HDL-C, LDL-C, ApoA1 and ApoB levels between different subgroups. The ApoA1 level was lower in the IPSS-R high-risk stratification group than that of the IPSS-R low-risk stratification group (P＜0.05). There were no significant differences in lipid levels between the different karyotype groups. The level of ApoA1 was lower in the TP53 mutant group than that in the non-TP53 mutant group (P＜ 0.05). Correlation analysis showed that ApoA1 level was positively correlated with body mass index (BMI, P＜0.05), and negatively correlated with patient age, percentage of bone marrow original cells, IPSS-R karyotype grouping, IPSS-R risk grouping and TP53 gene mutation (P＜0.05). The BMI level was lower in the low ApoA1 group than that of the high ApoA1 group (P＜0.05). The percentage of bone marrow original cells and TP53 gene mutation rate of MDS patients were higher in the low ApoA1 group than those in the high ApoA1 group (P＜0.05). Conclusion The plasma lipid level in MDS patients is significantly lower than that of healthy controls, and levels of ApoA1 varied significantly in different disease states, which may be associated with TP53 gene mutation. [ABSTRACT FROM AUTHOR]

Background: Posterior fossa malformation (PFM) is a relatively uncommon prenatal brain malformation. Genetic diagnostic approaches, including chromosome karyotyping, copy number variant (CNV) testing, and whole-exome sequencing (WES), have been applied in several cases of fetal structural malformations. However, the clinical value of appropriate genetic diagnostic approaches for different types of PFMs has not been confirmed. Therefore, in this study, we aimed to analyze the value of different combined genetic diagnostic approaches for various types of fetal PFMs. Methods: This retrospective study was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital. Fifty-one pregnant women diagnosed with fetal PFMs who underwent genetic testing in our hospital from January 1, 2017 to December 31, 2022 were enrolled; women with an isolated enlarged cisterna magna were excluded. All participants were categorized into two groups according to the presence of other abnormalities: isolated and non-isolated PFMs groups. Different combined approaches, including karyotype analysis, CNV testing, and trio-based WES, were used for genetic analysis. The detection rates of karyotype analysis, CNV testing, and WES were measured in the isolated and non-isolated groups. Results: In isolated PFMs, pathogenic/likely pathogenic (P/LP) CNVs were detected in four cases (36.36%, 4/11), whereas G-banding karyotyping and WES showed negative results. In non-isolated PFMs, a sequential genetic approach showed a detection rate of 47.5% (19/40); karyotyping revealed aneuploidies in five cases (16.67%, 5/30), CNV testing showed P/LP CNVs in five cases (16.13%, 5/31), and WES identified P/LP variants (in genes CEP20, TMEM67, OFD1, PTPN11, ARID1A, and SMARCA4) in nine cases (40.91%, 9/22). WES showed a detection rate of 83.33% (5/6) in fetuses with Joubert syndrome. Only six patients (five with Blake's pouch cyst and one with unilateral cerebellar hemisphere dysplasia) survived. Conclusions: We recommend CNV testing for fetuses with isolated PFMs. A sequential genetic approach (karyotyping, CNV testing, and WES) may be beneficial in fetuses with non-isolated PFMs. Particularly, we recommend WES as the first-line genetic diagnostic tool for Joubert syndrome. [ABSTRACT FROM AUTHOR]

Background: The lack of germ cells in the seminiferous tubules is a hallmark of Sertoli cell-only syndrome (SCOS), a leading cause of male infertility. Recently, stem cell therapy has gained attention as a possible method for treating this illness. Objectives: The aim of this study was to determine if stem cell treatment is effective for SCOS patients. Subjects and Methods: From 2020 to 2022, 87 males had been diagnosed with primary infertility owing to SCOS. The patients were evaluated in a thorough clinical manner, which included testing of their genes, hormone profiles, and testicular biopsies, among other things. The testes were injected with pure stem cells that had been taken from bone marrow. Semen analysis, hormone levels, and testicular volume were periodically evaluated over the 12-month follow-up period. Results: Following treatment, 69 patients (79.3% of the total) did not have sperm in their semen, whereas 18 patients (20.7% of the total) did. When compared to non-responders, respondents showed a statistically significant drop in FSH and LH levels and a rise in testosterone levels (P < 0.001). Hormonal changes were significantly different in the groups who responded and those that did not, and all responders had normal karyotyping and no AZF microdeletions. Conclusion: Hormonal improvements were seen in responding individuals, suggesting that stem cell therapy may be a viable option for treating SCOS. Nevertheless, a significant number of patients chose not to participate, underscoring the need for more studies to improve patient selection and treatment procedures. [ABSTRACT FROM AUTHOR]

The repeated pregnancies with 21 -trisomy syndrome in a phenotypically normal mother are rare, and the possibility of maternal chromosomal mosaic should be considered. We report a woman with normal phenotype who had a history of early embryo loss for 4 times, two of which the karyotypes were 47,XY,+21. The couple′s karyotypes were normal (counting 20 split phases). Both noninvasive prenatal testing (NIPT) and extended NIPT results refer to a high risk of trisomy 21, and the amniocentesis single nucleotide polymorphism array (SNParray) result was [arr(1-22)×2,(XN×1)], and the fetal amniotic fluid karyotype was 46,XN. The repeated peripheral blood chromosomes test for the couple (counting 50 split phases) was performed, the maternal chromosome karyotype was diagnosed as 47,XX,+21[4]/46,XX[46], with a mosaic ratio of 7%-8%. Maternal fluorescence in situ hybridization (FISH) assay in 100 counted cells showed 7 trisomy 21 cells, suggesting that 7% of the cells were trisomy 21. Fetal amniotic fluid FISH test found no 21-trisomy cell. A healthy baby girl was delivered by cesarean section at 40 +1 weeks of gestation. In this case, maternal karyotype of a mosaic 21 -trisomy cell/normal cell phenotype may contribute to the twice early pregnancy losses with 21-trisomy syndrome. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the detection of gene fusions in acute leukemia using targeted RNA sequencing and compares its effectiveness with traditional methods like karyotyping and RT-PCR. Gene fusions, which result from chromosomal rearrangements, are crucial for diagnosing and treating leukemia. Recent updates in diagnostic criteria emphasize the importance of identifying these gene fusions. Targeted RNA sequencing offers advantages such as rapid diagnosis, minimal training requirements, and cost-effectiveness, making it a practical method in clinical settings. Our findings suggest that targeted RNA sequencing can accurately identify gene fusions, potentially benefiting nearly half of leukemia patients and improving diagnostic precision. This method may significantly impact the research community by providing a reliable and efficient tool for leukemia diagnosis. Gene fusions are key drivers in acute leukemia, impacting diagnosis and treatment decisions. We analyzed 264 leukemia patients using targeted RNA sequencing with conventional karyotyping and reverse transcription polymerase chain reaction (RT-PCR). Leukemic fusions were detected in 127 patients (48.1%). The new guidelines introduced additional diagnostic criteria, expanding the spectrum of gene fusions. We discovered three novel fusions (RUNX1::DOPEY2, RUNX1::MACROD2, and ZCCHC7::LRP1B). We analyzed recurrent breakpoints for the KMT2A and NUP98 rearrangements. Targeted RNA sequencing showed consistent results with RT-PCR in all tested samples. However, when compared to conventional karyotyping, we observed an 83.3% concordance rate, with 29 cases found only in targeted RNA sequencing, 7 cases with discordant results, and 5 cases found only in conventional karyotyping. For the five cases where known leukemic gene rearrangements were suspected only in conventional karyotyping, we conducted additional messenger RNA sequencing in four cases and proved no pathogenic gene rearrangements. Targeted RNA sequencing proved advantageous for the rapid and accurate interpretation of gene rearrangements. The concurrent use of multiple methods was essential for a comprehensive evaluation. Comprehensive molecular analysis enhances our understanding of leukemia's genetic basis, aiding diagnosis and classification. Advanced molecular techniques improve clinical decision-making, offering potential benefits. [ABSTRACT FROM AUTHOR]

Deletion of the proximal long arm of chromosome 6 is a rare chromosomal disorder, which is typically characterized by intellectual disability, developmental delay and abnormal facial features. The genetic etiology of a case of multiple malformation fetus was reviewed. The patient underwent amniocentesis at the 21+1 week of gestation, following findings of multiple fetal malformations indicated by ultrasound and high risk of fetal chromosome 6 abnormality indicated by noninvasive prenatal testing (NIPT). Routine G-banding chromosome karyotype analysis and copy number variation sequencing (CNV-seq) were performed. At the same time, the chromosome karyotypes of the parents were detected. Routine G-banding chromosome karyotype analysis of amniotic fluid showed 46,XX,del(6)(q14q16); CNV-seq results of amniotic fluid showed 23.68 Mb deletion in 6q14.1q16.3(80960000-104640000) region. Combining the above results, it is considered that the deletion is the cause of multiple fetal malformations. CNV -seq proves valuable in identifying the break point of fetal chromosome abnormalities, providing a basis for predicting the risk of fetal malformation and subsequent genetic counseling and enriching the prenatal clinical manifestations of 6q deletion. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the prevalence of submicroscopic chromosomal abnormalities found on single nucleotide polymorphism array (SNP array) in pregnancies with either an absent or hypoplastic nasal bone. Methods: This retrospective study included 333 fetuses with either nasal bone hypoplasia or absence identified on prenatal ultrasound. SNP array analysis and conventional karyotyping were performed in all the subjects. The prevalence of chromosomal abnormalities was adjusted for maternal age and other ultrasound findings. Fetuses with either an isolated nasal bone absence or hypoplasia, those that had additional soft ultrasound markers, and those where structural defects were found on ultrasound were divided into three groups: A, B, and C, respectively. Results: Among the total cohort of 333 fetuses, 76 (22.8%) had chromosomal abnormalities, including 47 cases of trisomy 21, 4 cases of trisomy 18, 5 cases of sex chromosome aneuploidy, and 20 cases of copy number variations of which 12 were pathogenic or likely pathogenic. The prevalence of chromosomal abnormalities in group A (n = 164), B (n = 79), and C (n = 90) was 8.5%, 29.1% and 43.3%, respectively. The incremental yields by SNP-array compared with karyotyping in group A, B, and C were 3.0%, 2.5% and 10.7%, respectively (p > 0.05). Compared to karyotype analysis, SNP array detected an additional 2 (1.2%), 1 (1.3%), and 5 (5.6%) pathogenic or likely pathogenic CNVs in groups A, B, and C, respectively. In the 333 fetuses, the prevalence of chromosomal abnormalities in women with advanced maternal age (AMA) was significantly higher than that in non-AMA women, (47.8% vs. 16.5%, p < 0.05). Conclusion: In addition to Down's syndrome, many other chromosomal abnormalities are present in fetuses with abnormal nasal bone. SNP array can improve the prevalence of chromosomal abnormalities associated with nasal bone abnormalities, especially in pregnancies with non-isolated nasal bone abnormalities and advanced maternal age. [ABSTRACT FROM AUTHOR]

Mixed gonadal dysgenesis is caused by a variety of chromosome abnormalities, most commonly Y chromosome mosaicism. An 8-year-old boy presented with short stature for possible treatment with recombinant growth hormone. He had a history of mixed gonadal dysgenesis (hypospadias, bilateral cryptorchidism, processus vaginalis, and dysplastic immature uterus) and a series of corrective surgeries. At 14 months of age, chromosomal karyotyping revealed 46,X,+mar. Upon presentation, lab testing was consistent with the male phenotype at prepuberty. Fluorescence in situ hybridization revealed 45,X[2]/46,X,der(Y).ish psu idic(Y)(q11.2)(SRY++,DYZ3++)[38] karyotype. A literature review identified eight case reports of mixed gonadal dysgenesis associated with 45,X/46,X,idic(Y)(q11.2). Neither sex phenotype nor short stature correlated with the 46,X,idic(Y)(q11.2) mosaic ratio.

Transient Abnormal Myelopoiesis (TAM) is a transient haematological condition observed in children with Down syndrome during their neonatal period. Spontaneous resolution without any specific treatment is the rule, and the condition is known to occur exclusively in association with trisomy 21. Around 10% of Down syndrome babies are known to be affected by TAM, and 20-30% of these babies are known to develop acute myeloid leukaemia, of the megakaryoblastic type, in their later lives. Multisystem involvement is known in this condition. The present case of TAM is a two-day-old newborn female baby, born out of full-term gestation, presented with respiratory distress along with congenital pneumonia, hepatosplenomegaly, and mild ascites. The baby also had significant pulmonary hypertension, an Atrial Septal Defect (ASD), and non restrictive Patent Ductus Arteriosus (PDA). A significant increase in the total leukocyte count was seen, accompanied by thrombocytosis and 72% blastoid cells. Then, using karyotyping, Trisomy 21 was verified. 35% of the blasts had megakaryoblastic differentiation, according to flow cytometry. Hence, before diagnosing congenital leukaemia based on finding excess blasts in the peripheral smear of a newborn, karyotyping has to be done to look for possible trisomy 21. It can be an incidental finding, as in the present case, without prior clinical suspicion of Down syndrome.

Abstract Objective This study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism. Methods For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD). Results Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal. Conclusion In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7.

Abstract This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

Ring chromosome 20 syndrome is a rare genetic disorder characterized by non-convulsive status epilepticus (NCSE) attacks, leading to prolonged confusional states of varying intensity. It is often accompanied by electroencephalography (EEG) changes, such as long-lasting slow waves and occasional spikes, primarily over the frontal lobes, as well as focal seizures with visual hallucinations, cognitive impairment, and behavioral problems. Although clinical suspicion, typical EEG abnormalities, and network disorders revealed by functional neuroimaging method aid in diagnosis, karyotyping remains essential. Seizures are typically drug-resistant although some limited success has been reported with certain anti-seizure drugs. In this report, we present the case of a patient with previously frequent drug-resistant NCSE periods characterized by prolonged confusional states and frightening visual hallucinations. Treatment with lacosamide partially decreased the frequency of seizures. In addition, positron emission tomography/computed tomography (PET/CT) imaging revealed hypometabolism in the frontal and parietal regions of the brain. In patients with drug-resistant and early frightening hallucinations, consideration of the ring 20 chromosome anomaly is crucial. PET/CT imaging may demonstrate hypometabolism in the parietal and frontal lobes, potentially associated with the hallucinations and epileptogenesis of the syndrome. Lacosamide may be a viable option for reducing seizures in Ring chromosome 20 syndrome.

In the field of cytogenetics, chromosome image analysis plays a critical role in the diagnosis of various genetic disorders and cancers. As the gold standard, chromosome image analysis focuses on metaphase images, as all chromosomes become distinctly visible during this phase of cell mitosis. However, not all the detected metaphases are suitable for karyotyping due to chromosome stickiness. Therefore, cytogenetics selects the analyzable metaphase images by exploring all the samples. Since this task is very time-consuming, efforts have been made to automate the analyzable metaphase selection step of karyotyping. Nevertheless, these studies have drawbacks, such as utilizing hand-crafted features, requiring expert-provided candidate metaphase cell regions for classification, and demanding 100X magnified microscopic images. In this study, a novel two-staged deep-learning based workflow is presented for automatic detection of analyzable metaphase cells. The proposed model operates on 10X magnified images while omitting traditional image processing steps that are used in state-of-the-art methods for determining candidate metaphases. In the first stage, Faster R-CNN method with Inception V2 architecture is used to directly identify analyzable metaphases in specimen slide images. The second stage involves analyzable metaphase image verification based on VGG19 model. To assess the success of the proposed method, we also evaluate two state-of-the-art techniques: YOLOv8 and EfficientNet algorithms. The results obtained with different combination options achieved true positive rates up to 98.5% while reducing false positive rates to 0.0001. This study is the first to introduce an end-to-end deep learning-based approach for analyzable metaphase detection. Comparing it with existing literature, it becomes evident that the proposed approach achieves an optimal balance between true positive rates and false positive rates, maintains efficient processing speed, and eliminates the need for high-magnification image acquisition. All these factors play imperative roles in the clinical usage of the system. [ABSTRACT FROM AUTHOR]

Objective: This study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism. Methods: For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD). Results: Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal. Conclusion: In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7. [ABSTRACT FROM AUTHOR]

The etiology of spontaneous abortion is complex, including embryonic factors, maternal factors, environmental factors and abnormal immune function. Approximately 50% ～60% abortions are related to fetal chromosomal abnormalities. We reported a case of twice spontaneous abortion. The couple were subject to both chromosome karyotype and fluorescence in situ hybridization (FISH) analysis. None of obvious abnormality was observed in the wife, while chromosome karyotype result showed 46,XY,t(1;11)(p36.2;q24) in the husband. The balanced translocation of t(1;11) carried by the husband may be the reason for recurrent spontaneous abortion in this family. The case indicated the application value of FISH technology in the verification of suspect subtelomeric rearrangements. [ABSTRACT FROM AUTHOR]

The adjacent -2 segregation is a rare separation mode in the gametic formation of balanced translocation carriers. A fetus with severe fetal growth restriction (FGR) and chromosomal abnormalities is reported, and the prenatal diagnosis was performed by G -banding karyotype analysis, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH), quantitive fluorescent polymerase chain reaction (QF-PCR). The CMA result of amniotic fluid was arr[hg19]18p11.32q11.2(141,354-21,994,637)×3, 21q11.2q21.3(15,502,777- 29,700,071)×1; Refer to the CMA results, the fetal karyotype was described as 46,XX, +der(18)t(18;21) (q11.2; q22.1),-21. In order to verify the source of abnormal karyotype, the chromosomes of parents′ peripheral blood were detected. The father′s karyotype was 46,XY,t(18;21)(q11.2;q22.1), and the pregnant woman had normal karyotype. FISH results showed that the amniotic fluid cells had two normal 18 chromosomes, one normal 21 chromosome and one derived 18 chromosome, and that the father was a cross-translocation carrier of the 18p and 21p. To rule out the possibility that the fetus′s two normal chromosomes 18 were uniparental disomy, this study used the results of identification of maternal blood contamination, and the results of short tandem repeat(STR) test confirmed that only one of the two normal chromosome 18 came from the mother. Therefore, the application of multiple detection techniques in the diagnosis of rare separation methods such as adjacent-2 segregation can help doctors to provide accurate prenatal genetic counseling for those balanced translocation carriers, and to identify the types of chromosomal abnormalities in their fetuses. [ABSTRACT FROM AUTHOR]

Objective To investigate the application value and significance of low depth genome-wide copy number variation sequencing (CNV-seq) in the diagnosis of genetic etiology of recurrent spontaneous abortion by comparing differences of chromosome abnormalities and copy number variation in recurrent spontaneous abortion (RSA) and sporadic abortion (SA). Methods A total of 402 aborted tissue from 158 RSA patients and 244 SA patients were collected for CNV-seq detection. The chromosome karyotypes in peripheral blood of couples with suspected chromosomal abnormality were detected with high resolution. Results In 402 samples, 2 cases were failed, and the detection success rate was 99.5% (400/402). A total of 238 (59.5%) chromosome abnormalities were detected in 400 samples, including 212 (89.1%) chromosome number abnormalities, 25 (10.5%) pathogenic copy number variation and 1 (0.4%) uniparental disomy. There were no significant differences in the overall incidence rate of chromosome abnormality, aneuploid abnormality and triploid between the two groups. The proportion of pathogenic copy number variation in chromosome abnormalities was significantly higher in the RSA group than that in the SA group (P＜0.05). A total of 4 balanced translocation carriers were detected by high-resolution peripheral blood karyotype analysis. During the age range of 35-39, the rate of chromosomal abnormality was significantly higher in the SA group than that in the RSA group (P＜0.05). In both the RSA group and the SA group, the chromosomal abnormality rate in the first trimester abortion was significantly higher than that in the second trimester abortion, while the rate of POCs chromosomal abnormalities was higher in the SA group than that in the RSA group in the first trimester abortion (P＜0.05). Conclusion CNV-seq can accurately diagnose the numerical chromosomal abnormalities and the duplication/deletion of chromosome fragments in embryos, which is equally important in the genetic etiology diagnosis of RSA and SA, and can provide sufficient evidence for the guidance of reproduction. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance. [ABSTRACT FROM AUTHOR]

Karyotyping requires chromosome instances to be segmented and classified from the metaphase images. One of the difficulties in chromosome segmentation is that the chromosomes are randomly positioned in the image, and there is a great chance for chromosomes to be touched or overlap with others. It is always much easier for operators and automatic programs to tackle images without overlapping chromosomes than ones with largely overlapped chromosomes. In order to reduce the processing difficulty, adding a smart image selection procedure ahead of segmentation is practical and necessary. In this paper, we introduce the Smart Karyotyping Image Selection (SKIS) based on Commonsense Knowledge Reasoning. The initial experiment demonstrates that the proposed approach can select the expected images based on reasoning and benefit following karyotyping processes. [ABSTRACT FROM AUTHOR]

Purpose: Fetal karyotyping is commonly used to detect chromosomal abnormalities in high-risk pregnancies. Our study is intended to evaluate the results of fetal karyotyping performed in our laboratory for six years and to determine the frequency of chromosomal abnormalities, thus revealing their clinical significance. Materials and Methods: The cytogenetic results of 661 prenatal samples with an indication for invasive prenatal procedures (amniocentesis, cordocentesis) who had a chromosome analysis and FISH testing between February 2013 and March 2019 were analyzed in our study. Results: A total of 72 (10.8%) abnormal fetal karyotypes were observed in the study group. Trisomy 21 was the most common numerical aberration (29%, n = 23), followed by trisomy 18 (16%, n = 13), trisomy 13 (2.6%, n = 2), triploid (2.6%, n = 2), sex chromosome aneuploidies (5.2%, n = 4), and rare mosaic autosomal aneuploidies (2.6%, n = 2). Inversions (16%, n = 13), inherited translocations (7.8%, n = 6), unbalanced/de novo translocations (6.5%, n = 5), d eletions (5.2%, n = 4), additional chromosomes (1.3%, n = 1), isochromosomes (1.3%, n = 1), and derivative chromosomes (1.3%, n = 1) were identified as structural abnormalities. Of the 18 cases that underwent FISH testing, trisomy 18 was detected in 1 case and tetrasomy 12p was detected in 1 case. Conclusion: Fetal karyotyping is still an effective and valuable method in the diagnosis of fetal anomalies and provision of effective genetic counseling. In addition, fetal karyotyping should be supported by complementary methods and advanced technologies for accurate and rapid prenatal genetic diagnosis. [ABSTRACT FROM AUTHOR]

Leukemia-associated structural chromosomal abnormalities (SCA) can be identified either by karyotyping or interphase-fluorescence in-situ hybridization (i-FISH) assays. Both karyotyping and i-FISH on mononuclear cell suspension are time, resource, and manpower-consuming assays. In this study, we have compared the results of specific leukemia-associated SCAs identified by i-FISH on air-dried bone marrow (BM)/peripheral blood (PB) smears and BM karyotyping. The study was conducted among pediatric patients (age ≤ 18 years) diagnosed with acute leukemias between January 2018 to December 2022. The results of i-FISH on air-dried BM/PB smears and BM-karyotyping for our SCA of interest (BCR::ABL1, ETV6::RUNX1, TCF3::PBX1, KMT2A rearrangement, RUNX1::RUNX1T1, CBFB::MYH11, and PML::RARA) were entered in a contingency table and the agreement of results was calculated. The strength of agreement was assessed by Cramer's V test. Among 270 patients, SCA of interest was identified among 26% and 17% of patients by i-FISH on air-dried smears and karyotyping, respectively. Excluding 53 patients with metaphase failure, the remaining 217 patients had 92% agreement (Cramer's V of 0.931 with p < 0.000) between the results for specific SCAs identified by both techniques. On excluding samples with cryptic cytogenetic aberrancies, there was 99% agreement (Cramer's V of 0.953 with p < 0.000) for gross SCA identified by both techniques. In addition, i-FISH on air-dried smears identified SCA in 30% of patients with metaphase failure. I-FISH on air-dried PB/BMA smears is a less-labor and resource-consuming assay. It can be considered an efficient alternative to conventional karyotyping for identifying specific SCA of interest in under-resourced laboratories. [ABSTRACT FROM AUTHOR]

Karyotyping is the process of pairing and ordering human chromosomes from metaphase chromosomal images depending on their size, centromere position, and banding patterns. It is used to analyze human chromosomes for various genetic disorders especially during prenatal screenings. Since manual karyotyping is a labor‐intensive and a time‐consuming task, developing an automatic or semi‐automatic computer‐assisted karyotyping system is the need of the hour. The proposed karyotyping system aims to detect human chromosomes (22 pairs of autosomes and one pair of sex chromosome) from the microscopic metaphase images which is followed by separation of overlapped chromosomes. Extracted chromosomes are first classified into seven Denver groups (A to G) followed by classifying individual chromosomes within their Denver group. Then the classified chromosome pairs are used to create a karyotype with the assistance of cytologists or by using estimated chromosome length as cytogenetic parameter. A total of 234 chromosomal images from two different public datasets are used for experimentation. Human chromosomes in the microscopic metaphase images are detected using faster regions with convolutional neural networks (Faster R‐CNN) combined with Inception v2. Then convexity defect algorithm is preferred for separation of overlapped chromosomes. The detected chromosomes are classified using the proposed two‐step approach in which Inception v3 model is used. Then the classified chromosome pairs are used to create a karyotype with the assistance of cytologists or by using estimated chromosome length as cytogenetic parameter. Faster R‐CNN model gives a detection accuracy of 98.53%. Denver group classification with the two‐step approach provides a better accuracy of 84.59% when network is trained for 64 902 epochs. Faster R‐CNN outperforms in detection and works faster as it searches chromosomes within the regional proposals. The two‐step classification approach gives better classification accuracy. The proposed approach also works very well for overlapping chromosomes due to use of convexity defects algorithm. The classified chromosome pairs are useful tools for the cytologists to create a karyotype with minimal efforts. [ABSTRACT FROM AUTHOR]

Objective: To explore the etiological genetics diagnosis of fetuses with craniofacial malformations (CFMs) using chromosomal microarray analysis (CMA). Methods: Enrolled in this study were 72 pregnancies with fetal CFMs who came to Quanzhou Women′s and Children′s Hospial for etiology diagnosis from January 2017 to March 2023. Among them, 46 cases had the isolated CFMs and 26 cases also had other structural anomalies. In addition, 45 cases performed amniocentesis and carried out karyotype analysis and CMA, and the rest 27 cases only conducted CMA using fetal abortive tissue. Results: In the 45 cases that performed karyotype analysis, a trisomy 18 and a 47,XXY were diagnosed, with an abnormal detection rate of 4.44% (2/45). In the total 72 enrolled subjects that conducted CMA, 4 cases of aneuploid, 3 cases of pathogenic copy number variants (pCNVs), and 11 cases of variants of unknown significance were diagnosed, with an abnormal detection rate of 9.72% (7/72). In addition, the sub -group study indicated that the abnormal detection rate in the non -isolated CFMs group was significantly higher than that in the isolated CFMs group (26.92% vs. 0.00%，P＜0.001). Conclusions: For those fetuses with CFMs indicated by prenatal ultrasound, the subsequent CMA would be helpful to clarify the genetic etiology of CFMs. [ABSTRACT FROM AUTHOR]

Cell lines are important in vitro models to answer biological mechanisms with less genetic variations. The present study was attempted to develop a cell line from rainbow trout, where we obtained a cell line from the heart, named "RBT‐H." The cell line was authenticated using karyotyping and cytochrome c oxidase subunit I (COI) gene sequencing. The karyotype demonstrated diploid chromosome number (2n) as 62 and the sequence of partial COI gene was 99.84% similar to rainbow trout COI data set, both suggesting the origin of RBT‐H from the rainbow trout. The heart cell line was mycoplasma‐free and found to be refractory to infection with the Tilapia lake virus. The RBT‐H cell line is deposited in the National Repository of Fish Cell Line (NRFC) at ICAR‐NBFGR, Lucknow, India, with Accession no. NRFC0075 for maintenance and distribution to researchers on request for R&D. [ABSTRACT FROM AUTHOR]

Introduction: Hyperdiploidy (more than 50 chromosomes) is an important cytogenetic abnormality found in B cell acute lymphoblastic leukemia (B cell ALL). The presence of hyperdiploidy > 50 is considered to be a good prognostic marker since it has increased sensitivity to standard chemotherapy. Patients with hyperdiploidy have the longest disease-free survival compared with any other cytogenetic group. Aim of study: To estimate prevalence of hyperdiploid chromosomes in patients with B cell ALL through conventional karyotyping and Fluorescent in situ hybridization (FISH). Materials and methods: Retrospective study was done on 200 bone marrow samples diagnosed with B cell Acute lymphoblastic leukemia referred to Division of Human Genetics, Department of Anatomy, St. John's Medical college, Bangalore. Samples were subjected to standard protocol for karyotyping and FISH. Percentage of patients who had hyperdiploidy was calculated. Results: Out of 200 samples, 30 samples had hyperdiploidy accounting to 15% of total patients diagnosed with B cell ALL. Conclusion: Conventional cytogenetics and FISH play a very important role in detecting hyperdiploidy since it is vital in risk stratification and treatment in patients with B cell ALL.

Transient Abnormal Myelopoiesis (TAM) is a transient haematological condition observed in children with Down syndrome during their neonatal period. Spontaneous resolution without any specific treatment is the rule, and the condition is known to occur exclusively in association with trisomy 21. Around 10% of Down syndrome babies are known to be affected by TAM, and 20-30% of these babies are known to develop acute myeloid leukaemia, of the megakaryoblastic type, in their later lives. Multisystem involvement is known in this condition. The present case of TAM is a two-day-old newborn female baby, born out of full-term gestation, presented with respiratory distress along with congenital pneumonia, hepatosplenomegaly, and mild ascites. The baby also had significant pulmonary hypertension, an Atrial Septal Defect (ASD), and non restrictive Patent Ductus Arteriosus (PDA). A significant increase in the total leukocyte count was seen, accompanied by thrombocytosis and 72% blastoid cells. Then, using karyotyping, Trisomy 21 was verified. 35% of the blasts had megakaryoblastic differentiation, according to flow cytometry. Hence, before diagnosing congenital leukaemia based on finding excess blasts in the peripheral smear of a newborn, karyotyping has to be done to look for possible trisomy 21. It can be an incidental finding, as in the present case, without prior clinical suspicion of Down syndrome. [ABSTRACT FROM AUTHOR]

Abstract Background Individuals with X chromosomal translocations, variable phenotypes, and a high risk of live birth defects are of interest for scientific study. These characteristics are related to differential breakpoints and various types of chromosomal abnormalities. To investigate the effects of X chromosome translocation on clinical phenotype, a retrospective analysis of clinical data for patients with X chromosome translocation was conducted. Karyotype analysis plus endocrine evaluation was utilized for all the patients. Additional semen analysis and Y chromosome microdeletions were assessed in male patients. Results X chromosome translocations were detected in ten cases, including seven females and three males. Infantile uterus and no ovaries were detected in case 1 (FSH: 114 IU/L, LH: 30.90 mIU/mL, E2:

Background Cytogenetics is a fundamental examination in the course and management of myelodysplastic syndrome (MDS) since it is widely used as a diagnostic and prognostic indicator for the disease. Some cytogenetic profiles are associated with a higher risk of acute myeloid leukemia (AML) transformation. This is the first study to evaluate the cytogenetic profile of Indonesian patients with MDS. Methods This prospective cohort study was conducted at the Cancer Center and several other referral hospitals. Patients with primary MDS aged >18 years were included in the study. Clinical examination, peripheral blood smear, and bone marrow aspiration were performed, followed by cytogenetic examination. The results were further categorized into revised international prognostic scoring system (IPSS-R) scores, and cytogenetic profiles were descriptively presented. Patients were followed up for one year to evaluate AML transformation. Results A total of 28 MDS patients, aged 66±12 years, were included in this study. The majority of the patients were male (n=17;60.7%), aged 65 years or above (n=19;67.9%), diagnosed with MDS-MLD (n=14;50%), and had an intermediate cytogenetic group (n=4;14.3%). The IPSS-R score was high in 6 (21.4%) patients and very high risk in 3 (10.7%) patients. During one-year follow-up, AML transformation occurred in 3 (10.7%) patients, and 10 (35.7%) patients ceased. Monosomy 7 was observed in 6 (21.4%) patients but in one metaphase each. Deletion of chromosome 5 (del(5)(q31)), del (16)(q21.1), and del (16)(q11.2) were found in a male patient with MDS-EB1. Conclusions Monosomy 7 and deletion of chromosome 5 have been identified in Indonesian patients with MDS. MDS-EB has the highest risk of AML transformation.

Aim: To study the role of genetics in human infertility. Materials and methods: We collected 60 male and 41 female blood samples from infertile couples and carried out a cytogenetic study in both males and females, whereas molecular study was done in only male subjects. Standard Giemsa banding karyotyping protocol was followed for the cytogenetic study. For azoospermia factor (AZF) microdeletion studies, deoxyribonucleic acid (DNA) isolation was followed by multiplex polymerase chain reaction (PCR) using AZF-specific sequence tagged site (STS) markers. Results: In the female cytogenetic study, no structural or chromosomal abnormalities were found; three (7.31%) had polymorphic variants. In males, one (1.6%) had autosomal structural 46, XY, t (3; 17) (p25; q22), one (1.6%) had sex chromosomal numerical abnormalities 47, XXY (12)/46, XX (8) and four (6.66%) had the polymorphic variant. Two males and two females had 9qh+ with other normal chromosomal constitutions. In the same way, two other types of polymorphism were also observed, that is, 21pS+ in one male and one female, whereas 22pS+ was observed in one male subject. The translocation 46, XY, t (3; 17) (p25; q22) we have found is unique. In male blood samples, we studied six gene mutations named AZFa (sy84), AZFa (sy86), AZFb (sy127), AZFb (sy134), AZFc (sy254), and AZFc (sy255). We have observed deletions in eight subjects with a microdeletion frequency of 13.33%, where seven (87.5%) were azoospermic, and one (12.5%) was oligozoospermic. Most found microdeletions were AZFb (sy127) in three males and AZFb (sy134) in three males. AZFa (sy86) and AZFa (sy254) deletions were found in one male. Conclusion: As per our knowledge, there is one novel translocation 46, XY, t (3; 17) (p25; q22) in one male patient from our research. We have also found AZF microdeletions in oligozoospermic and azoospermic patients. The results indicate the importance of karyotyping and microdeletion screening in chromosome Y for infertile couples before advising them of costlier treatments. Clinical significance: The present investigation is a valuable consideration for prognosis, which can be helpful for counseling couples and minimizing the potential risk of transmission of genetic abnormalities to future generations. [ABSTRACT FROM AUTHOR]

Ring chromosome 20 syndrome is a rare genetic disorder characterized by non-convulsive status epilepticus (NCSE) attacks, leading to prolonged confusional states of varying intensity. It is often accompanied by electroencephalography (EEG) changes, such as long-lasting slow waves and occasional spikes, primarily over the frontal lobes, as well as focal seizures with visual hallucinations, cognitive impairment, and behavioral problems. Although clinical suspicion, typical EEG abnormalities, and network disorders revealed by functional neuroimaging method aid in diagnosis, karyotyping remains essential. Seizures are typically drug-resistant although some limited success has been reported with certain anti-seizure drugs. In this report, we present the case of a patient with previously frequent drug-resistant NCSE periods characterized by prolonged confusional states and frightening visual hallucinations. Treatment with lacosamide partially decreased the frequency of seizures. In addition, positron emission tomography/computed tomography (PET/CT) imaging revealed hypometabolism in the frontal and parietal regions of the brain. In patients with drug-resistant and early frightening hallucinations, consideration of the ring 20 chromosome anomaly is crucial. PET/CT imaging may demonstrate hypometabolism in the parietal and frontal lobes, potentially associated with the hallucinations and epileptogenesis of the syndrome. Lacosamide may be a viable option for reducing seizures in Ring chromosome 20 syndrome. [ABSTRACT FROM AUTHOR]

Background: The purpose of the current study was to report a case with 45,X/46,XY/46,X,idic(Yp) mosaicism showing the male phenotype with mixed gonadal dysgenesis. Case Presentation: A 27 year-old individual, phenotypically male, presented with azoospermia and a micropenis. Both testes were not visualized in the scrotal sac. Due to the presence of a small-sized uterus, the individual was referred to the KSHEMA Center for Genetic Services for chromosomal analysis. Karyotyping revealed a mosaic karyotype of 45,X[44]/46,XY[5]/46,X,idic(Yp)[1]. This finding was further confirmed through fluorescent in situ hybridization (FISH) analysis. The individual's mosaic karyotype consisted of three cell lines, with a higher proportion of the 45,X cell line and lower proportions of the idic(Yp) and 46,XY cell lines. It is worth noting that this mosaic condition in postnatal peripheral blood has not been reported in the literature thus far. Conclusion: The case report demonstrated the importance of performing karyotype and FISH analysis in understanding genetic defects including mosaicism and other chromosomal aberrations, which can influence not only growth and puberty but also sexual development and maturation. Hence, performing cytogenetic and molecular cytogenetic analysis will help clinicians to take a further step in understanding and managing the condition. [ABSTRACT FROM AUTHOR]

Background: Individuals with X chromosomal translocations, variable phenotypes, and a high risk of live birth defects are of interest for scientific study. These characteristics are related to differential breakpoints and various types of chromosomal abnormalities. To investigate the effects of X chromosome translocation on clinical phenotype, a retrospective analysis of clinical data for patients with X chromosome translocation was conducted. Karyotype analysis plus endocrine evaluation was utilized for all the patients. Additional semen analysis and Y chromosome microdeletions were assessed in male patients. Results: X chromosome translocations were detected in ten cases, including seven females and three males. Infantile uterus and no ovaries were detected in case 1 (FSH: 114 IU/L, LH: 30.90 mIU/mL, E2: < 5.00 pg/ml), and the karyotype was confirmed as 46,X,t(X;22)(q25;q11.2) in case 1. Infantile uterus and small ovaries were both visible in two cases (FSH: 34.80 IU/L, LH: 17.06 mIU/mL, E2: 15.37 pg/ml in case 2; FISH: 6.60 IU/L, LH: 1.69 mIU/mL, E2: 23.70 pg/ml in case 3). The karyotype was detected as 46,X,t(X;8)(q13;q11.2) in case 2 and 46,X,der(X)t(X;5)(q21;q31) in case 3. Normal reproductive hormone levels and fertility abilities were found for cases 4, 6 and 7. The karyotype were detected as 46,X,t(X;5)(p22.3;q22) in case 4 and 46,X,der(X)t(X;Y)(p22.3;q11.2) in cases 6 and 7. These patients exhibited unremarkable clinical manifestations but experienced a history of abnormal chromosomal pregnancy. Normal phenotype and a complex reciprocal translocation as 46,X,t(X;14;4)(q24;q22;q33) were observed in case 5 with a history of spontaneous abortions. In the three male patients, multiple semen analyses confirmed the absence of sperm. Y chromosome microdeletion and hormonal analyses were normal. The karyotypes were detected as 46,Y,t(X;8)(q26;q22), 46,Y,t(X;1)(q26;q23), 46,Y,t(X;3)(q26;p24), respectively. Conclusions: Our study provides insights into individuals with X chromosome translocations. The clinical phenotypes are variable and unpredictable due to differences in breakpoints and X chromosome inactivation (XCI) patterns. Our results suggest that physicians should focus on the characteristics of the X chromosome translocations and provide personalized clinical evaluations in genetic counselling. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies diagnosed on Ultrasound scan, autopsy plays a vital role in confirming the diagnosis and many times gives information regarding additional malformations. Autopsy on dead fetuses/infants helps the parents by giving information regarding the recurrence risk of fetal anomaly. This study confirms the utility of fetal autopsy in identifying the cause of fetal loss which will indicate the need in genetic counseling of the couple. Aim: The study is done to record the incidence of congenital malformations in Fetal Autopsy. Details are collected from the department of Obstetrics and Gynecology. Methodology: A total of 98 fetal autopsies were done in the department of Pathology in a tertiary care teaching hospital, South India from the period of June 2015 to May 2020. Results: In 98 autopsies performed, 90 were fetal deaths and 8 neonatal deaths. Out of 62 autopsies on male fetuses, 22 had congenital malformations and of 36 autopsies on female fetuses, 14 had congenital malformations. Congenital anomalies were commonest in the birth weight group of <1000 gms, accounting for 28 cases. Most of the fetal deaths occurred in mothers with age group of 21-30 accounting to 27 cases out of 72 autopsies. Incidence of congenital anomalies was highe st in primigravida. Congenital malformations were seen in 36 cases which accounted for 36.7% of fetal and early neonatal deaths. Malformations of the central nervous system (33.3%) were the most common. Neural tube defects like anencephaly and spina bifida were seen in 8 cases. The second most common anomalies were encountered in Gastrointestinal system (19.4%), followed by genito-urinary system (13.8%) and cardiovascular system (8.3%). Tracheo esophageal fistula was the only case seen involving the respiratory system. Rare cases like Prune belly syndrome, Jarcho Levin syndrome were observed. Two cases of cystic hygroma and one case of Phocomelia with a history of Thalidomide intake by the mother were seen. Conclusion: Due to financial constraints only karyotyping was performed in the present study. Further studies including molecular biology should be carried out to identify more cases with congenital anomalies so that proper genetic counseling can be given to the parents to avoid subsequent anomalous births. [ABSTRACT FROM AUTHOR]

Infertility is a failure to get pregnant after one year of sexual intercourse without using contraception. The causes of infertility, especially in men, are very complex, including the aging process, hormonal disorders, lifestyle, environment, metabolic disease, and genetic problems. One of the most difficult causes in male infertility is genetic problems. In this case, a 35 year old man was reported with primary infertility and often experienced premature ejaculation and even anejaculation. Previously, the patient had repeatedly consulted about his condition at other fertility service centers. The conclusion obtained was that the patient had azoospermia with bilateral varicoceles and had been given hormone therapy but had not yet found a final diagnosis so the patient was still confused about what had happened to him. At the first visit the patient underwent a sperm analysis and the results were azoospermia. Then, based on the results of the history and physical examination, which indicated hypogonadism, a Y chromosome microdeletion examination was carried out, and a deletion was found in the AZFc region, which is a marker of infertility that causes spermatogenic failure. The examination was continued with karyotyping, the result was 47.XXY, consistent with the condition of Klinefelter syndrome. Conclusion: Carry out a karyotyping examination if you find signs and symptoms that suggest primary hypogonadism in male infertility. This can be done to streamline the diagnostic approach time in patients with primary hypogonadism, especially those with infertility. [ABSTRACT FROM AUTHOR]

Background: Cytomolecular genetic laboratory techniques have developed from conventional G-banding karyotyping to whole genome sequencing. Although resolution has greatly increased, various cytogenetic techniques have their advantages and limitations in detecting genomic variations. Methods: We compared the chromosomal abnormalities detected by G-banding karyotyping and SNP-based microarray testing in 62 patients from July 2020 to December 2022. We analyzed their difference according to chromosomal abnormalities, including numerical and structural and others. Results: Of the 62 patients, 28 patients showed chromosomal aberration detected in one or more of the two test methods. Aneuploidy was detected in both methods, while gain and loss less than 3 Mb were only detectable by the microarray. G-banding karyotyping is fundamental to detect structural chromosome rearrangement such as inversions, ring chromosomes, and translocations, but additional breakpoint or unknown origin materials information obtained from microarray. Loss of heterozygosity was only detectable in microarray, and mosaicism had limitations in both G-banding karyotyping and microarray. Conclusions: Various disease cause genomic structural variants, it is very important to detect this. We showed discordance between G-banding karyotyping and SNP based microarray in clinical laboratory. It can be helpful to clinical physicians to decide which diagnostic tool to use. [ABSTRACT FROM AUTHOR]

Background: Menstruation is an important physiological function of the female reproductive system. The absence of menstruation is called amenorrhea. Many genetic and nongenetic causes are responsible for primary or secondary amenorrhea. This study aimed to determine the types chromosomal abnormalities among patients with primary or secondary amenorrhea. Methods: It was a cross-sectional study conducted in the Department of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka, from September 2019 to August 2021. A total of 115 women who had come for a karyotype test with complaints of pathological amenorrhea were purposively selected. One hundred five cases presented with primary amenorrhea, and 10 cases presented with secondary amenorrhea. Karyotype analysis in peripheral blood by G-banding was carried out using the standard method. Results: Among the 105 patients with primary amenorrhea, 53.3% of patients had a normal karyotype (46, XX), and 46.6% had chromosomal abnormalities (numerical or structural). Turner syndrome classic, 45, XO (16.2%) and 46, XY DSD (Disorders of Sexual Development) (11.4%) were the two most frequent chromosomal abnormalities found in the patients with primary amenorrhea. Among the 10 cases with secondary amenorrhea, seven patients had normal karyotype, and three patients had chromosomal abnormalities (2 had sex chromosomal abnormalities, and 1 had a structural abnormality of autosome). Conclusion: The study of chromosomal abnormalities will help in the early and accurate diagnosis of the underlying aetiology of primary or secondary amenorrhea. It will also help in the management and proper counselling of cases.

Chinese hamster ovary (CHO) cells are the primary host for manufacturing of therapeutic proteins. However, productivity loss is a major problem and is associated with genome instability, as chromosomal aberrations reduce transgene copy number and decrease protein expression. We analyzed whole-genome sequencing data from 11 CHO cell lines and found deleterious single-nucleotide variants in DNA repair genes. Comparison with primary Chinese hamster cells confirmed DNA repair to be compromised in CHO. Correction of key DNA repair genes by single-nucleotide variant reversal or expression of intact complementary DNAs successfully improved DNA repair and mitigated karyotypic instability. Moreover, overexpression of intact copies of LIG4 and XRCC6 in a CHO cell line expressing secreted alkaline phosphatase mitigated transgene copy loss and improved protein titer retention. These results show that correction of DNA repair genes yields improvements in genome stability in CHO, and provide new opportunities for cell line development for sustainable protein expression.