OBJECTIVE: Chromosome conformation-based karyotype analysis (C-MoKa) technology was used to test a couple who had experienced multiple adverse pregnancies in order to provide them with genetic counseling and reproductive guidance. METHODS: A couple presented at the Reproductive Medicine Center of the First Hospital of Lanzhou University in 2023 was selected as the study subject. Through C-MoKa testing, copy number variation sequencing (CNV-seq), and preimplantation genetic testing for aneuploidy (PGT-A), it was found that the couple's repeatedly miscarried fetuses and abnormal embryos exhibited highly similar chromosomal structural abnormalities. Using C-MoKa, the potential genetic abnormalities in both partners were traced, and reproductive guidance was provided based on the result. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-09). RESULTS: CNV-seq analysis of the couple's miscarriage fetal chorionic villi showed del(18)(q21.2q23)(28.90 Mb) and dup(13)(q31.2q34)(26.26 Mb). Chromosomal karyotyping analysis of both partners showed no abnormality. From 2024 to 2025, the couple underwent three rounds of PGT-A assisted reproduction. The first embryo test showed del(13)(q31.2q34)(26.77 Mb) and dup(18)(q21.2q23)(29.08 Mb). The second embryo test showed dup(13)(q31.2q34)(26.26 Mb) and del(18)(q21.2q23)(28.90 Mb). And the third embryo test results showed complex chromosomal abnormalities. In 2025, after genetic counseling, the couple had opted C-MoKa test, which has detected no abnormality in the wife, but a balanced 46,XY,t(13;18)(q31.2;q21.2) translocation in the husband. CONCLUSION As a high-throughput sequencing method based on the three-dimensional conformation of chromatin, C-MoKa has the advantages of high resolution and high accuracy, and can accurately detect balanced translocations with similar banding patterns. It has therefore offered a powerful new tool for chromosomal analysis.
Female ; Humans ; Male ; Pregnancy ; Abortion, Habitual/genetics* ; DNA Copy Number Variations ; Karyotyping/methods* ; Preimplantation Diagnosis ; Translocation, Genetic

OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene. METHODS: A retrospective analysis was carried out on the clinical data, treatment, and prognosis of seven AML patients with t(16;21)(p11;q22) FUS::ERG fusion gene admitted to Henan Children's Hospital between June 2015 and November 2024. Relevant literature was also reviewed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-102-001). RESULTS: Among 297 pediatric patients with AML, 7 cases (2.36%) were positive for the t(16;21)(p11;q22) FUS::ERG fusion gene, including 3 males and 4 females, with a median age of 11 years (range: 3 ~ 12 years). According to the FAB classification, these included 1 case of M2, 3 cases of M5, and 3 cases of AML-not otherwise specified (non-M3). All 7 patients were found to harbor the t(16;21)(p11;q22) translocation, with 3 cases showing additional chromosomal abnormalities. Immunophenotyping revealed universal expression of CD13, CD33, CD34, and CD117, with partial expression of CD56, CD4, CD64, CD123, CD15, CD38, CD11b, HLA-DR, cMPO, and CD16. One patient achieved complete remission (CR) after the first course of DAE (cytarabine + daunorubicin + etoposide) induction chemotherapy but relapsed and discontinued the treatment. Six patients received DAH (cytarabine + daunorubicin + homoharringtonine) induction therapy, of whom 2 achieved CR after two courses and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in an overall CR rate of 42.86%. Five children did not receive allo-HSCT and had a median overall survival of 9 months (range: 6 ~ 18 months). Two children who underwent transplantation achieved bone marrow morphological and molecular biological relapse at 6 and 9 months post-transplantation, respectively. After receiving combined chemotherapy and donor lymphocyte infusion, one child failed to achieve remission and died at 22 months post-transplantation, while the other has been followed up to date with positive fusion gene status. Their overall survival was 25 months and 30 months, respectively. CONCLUSION The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival.
Humans ; Male ; Child ; Female ; Leukemia, Myeloid, Acute/drug therapy* ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic ; Retrospective Studies ; RNA-Binding Protein FUS/genetics* ; Chromosomes, Human, Pair 16/genetics* ; Adolescent ; Child, Preschool ; Chromosomes, Human, Pair 21/genetics* ; Prognosis ; Treatment Outcome

OBJECTIVE: To apply optical genome mapping (OGM) technique for the analysis of genetic etiology in two rare families with complex chromosomal rearrangements (CCRs) and to provide precise reproductive guidance to them. METHODS: Two Chinese families diagnosed with chromosomal rearrangements by chromosomal microarray analysis (CMA) or whole-exome sequencing (WES) between June and December 2023 at the Affiliated Women and Children's Hospital of Ningbo University were selected as the study subjects. In both cases, unbalanced chromosomal translocations were suspected. Clinical data were collected, and peripheral blood from the couple, amniotic fluid sample and aborted fetal tissue was subjected to combined G-banding karyotyping and OGM for comprehensive genetic analysis. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2023-094). RESULTS: In family 1, the fetus was signaled to have abnormal chromosome 7 by non-invasive prenatal testing (NIPT), prompting amniocentesis and CMA detection. In family 2, a pregnancy loss had occurred at 10 weeks' gestation, and trio-WES was carried out. Both fetuses were found to harbor copy number variations (CNVs) suggestive of unbalanced CCRs. Further analysis with OGM has revealed that, in family 1, an unbalanced rearrangement involving chromosomes 7, 8, and 10 was carried by the fetus and the pregnant woman, which has formed der(8) and der(10) derivative chromosomes. In family 2, a maternal CCR was found, which involved chromosomes 2 and 13 with seven breakpoints, resulting in unbalanced fetal CNVs. After genetic counseling, family 1 opted to continue with the pregnancy, considering the woman's normal appearance and inheritance of the rearrangement. For both families remained to have a risk for unbalanced rearrangements in subsequent pregnancies, preimplantation genetic testing (PGT) was recommended. CONCLUSION In both families, the OGM has precisely delineated the genetic basis of fetal CNVs and mapped the maternal CCR breakpoints, providing critical insights for genetic counseling and reproductive decision-making.
Adult ; Female ; Humans ; Male ; Pregnancy ; Chromosome Aberrations ; Chromosome Disorders/genetics* ; Chromosome Mapping/methods* ; Genetic Testing/methods* ; Pedigree ; Prenatal Diagnosis/methods* ; Translocation, Genetic

OBJECTIVE: To explore a case of abnormal fetal development due to a rare paternal t(10;14)(p11.2;p11) translocation. METHODS: A fetus undergoing prenatal diagnosis at Northwest Women's and Children's Hospital on June 21,2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample of the fetus and peripheral venous blood samples of its parents were collected for chromosomal karyotyping and copy number variation (CNV) analysis. This study was approved by the Ethics Committee of the hospital (Ethics No.: 2024-132). RESULTS: Ultrasound scan at 23⁺⁴ gestational weeks revealed nasal bone dysplasia. Amniotic fluid analysis revealed that the fetus has a karyotype of 46,X?,der(14)t(10;14)(p11.2;p11)dpat, while its father had a 46,XY,t(10;14)(p11.2;p11) karyotype. No chromosomal abnormality was found in its mother. CNV analysis revealed that the fetus had a 30.46 Mb duplication in the 10p15.3-p11.23 region. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the duplication was classified as pathogenic. CONCLUSION By combining conventional cytogenetic methods with molecular techniques, the fetus was diagnosed with partial trisomy 10p syndrome caused by a rare paternal t(10;14)(p11.2;p11) translocation. Above finding holds significant clinical value for genetic counseling and prenatal diagnosis for the family.
Humans ; Translocation, Genetic ; Female ; Pregnancy ; Male ; Phenotype ; Chromosomes, Human, Pair 10/genetics* ; Adult ; Chromosomes, Human, Pair 14/genetics* ; Prenatal Diagnosis ; Karyotyping ; DNA Copy Number Variations/genetics* ; Fetus/abnormalities*

Humans ; Multiple Myeloma/genetics* ; Karyotyping ; Translocation, Genetic/genetics*

OBJECTIVE: To explore the genetic characteristics of a fetus with a high risk by maternal serum screening during the second trimester. METHODS: Genetic counseling was provided to the pregnant woman on March 22, 2020 at Henan Provincial People's Hospital. G-banded chromosomal karyotyping and array comparative genomic hybridization (aCGH) were carried out on the amniotic fluid sample and peripheral blood samples from the couple. RESULTS: The fetus and the pregnant woman were respectively found to have a 46,XX,der(6)t(6;14)(q27;q31.2) and 46,XX,t(6;14)(q27;q31.2) karyotype, whilst the husband was found to have a normal karyotype. aCGH analysis has identified a 6.64 Mb deletion at 6q26q27 and a 19.98 Mb duplication at 14q31.3q32.33 in the fetus, both of which were predicted to be pathogenic copy number variations. No copy number variation was found in the couple. CONCLUSION The unbalanced chromosome abnormalities in the fetus have probably derived from the balanced translocation carried by the pregnant woman. aCGH can help to determine the types of fetal chromosome abnormalities and site of chromosomal breakage, which may facilitate the prediction of fetal outcome and choice for subsequent pregnancies.
Pregnancy ; Female ; Humans ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Translocation, Genetic ; Chromosome Aberrations ; Fetus ; Prenatal Diagnosis

OBJECTIVE: To explore the genetic basis for a rare case of acute B-lymphocytic leukemia (B-ALL) with double Philadelphia chromosomes (Ph) and double derivative chromosome 9s [der(9)]. METHODS: A patient with double Ph and double der(9) B-ALL who presented at Shanghai Zhaxin Intergrated Traditional Chinese and Western Medicine Hospital in June 2020 was selected as the subject. Bone marrow morphology, flow cytometry, G-banding karyotyping, fluorescence in situ hybridization (FISH), genetic testing and chromosomal microarray analysis (CMA) were used to analyze bone marrow samples from the patient at various stages. RESULTS: At initial diagnosis, the patient's bone marrow morphology and flow immunotyping have both supported the diagnosis of B-ALL. G-banded karyotyping of the patient indicated double Ph, in addition with hyperdiploid chromosomes involving translocations between chromosomes 9 and 22. BCR-ABL1 fusion gene was positive. Genetic testing at the time of recurrence revealed presence of a heterozyous c.944C>T variant in the kinase region of the ABL1 gene. FISH showed a signal for ABL1-BCR fusion on both chromosome 9s. CMA showed that the mosaicism homozygosity ratio of chromosome 9 was about 40%, and the mosaicism duplication ratio of chromosome 22 was about 43%. CONCLUSION Since both der(9) homologs were seen in 40% of cells, the possible mechanism for the double der(9) in this patient may be similar to that of double Ph, which might have resulted from non-disjunction during mitosis in the Ph chromosome-positive cell clone.
Humans ; Philadelphia Chromosome ; In Situ Hybridization, Fluorescence/methods* ; China ; Chromosome Aberrations ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Translocation, Genetic ; Fusion Proteins, bcr-abl/genetics* ; Chromosomes, Human, Pair 9/genetics*

Humans ; Receptors, Chimeric Antigen/therapeutic use* ; DNA-Binding Proteins/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Cell- and Tissue-Based Therapy ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic

Large-scale genetic manipulation of the genome refers to the genetic modification of large fragments of DNA using knockout, integration and translocation. Compared to small-scale gene editing, large-scale genetic manipulation of the genome allows for the simultaneous modification of more genetic information, which is important for understanding the complex mechanisms such as multigene interactions. At the same time, large-scale genetic manipulation of the genome allows for larger-scale design and reconstruction of the genome, and even the creation of entirely new genomes, with great potential in reconstructing complex functions. Yeast is an important eukaryotic model organism that is widely used because of its safety and easiness of manipulation. This paper systematically summarizes the toolkit for large-scale genetic manipulation of the yeast genome, including recombinase-mediated large-scale manipulation, nuclease-mediated large-scale manipulation, de novo synthesis of large DNA fragments and other large-scale manipulation tools, and introduces their basic working principles and typical application cases. Finally, the challenges and developments in large-scale genetic manipulation are presented.
DNA ; Gene Editing ; Genetic Engineering ; Saccharomyces cerevisiae/genetics* ; Translocation, Genetic

OBJECTIVE: To carry out prenatal genetic testing for a fetus with de novo 46,X,der(X)t(X;Y)(q26;q11). METHODS: A pregnant woman who had visited the Birth Health Clinic of Lianyungang Maternal and Child Health Care Hospital on May 22, 2021 was selected as the study subject. Clinical data of the woman was collected. Peripheral blood samples of the woman and her husband and umbilical cord blood of the fetus were collected and subjected to conventional G-banded chromosomal karyotyping analysis. Fetal DNA was also extracted from amniotic fluid sample and subjected to chromosomal microarray analysis (CMA). RESULTS: For the pregnant women, ultrasonography at 25th gestational week had revealed permanent left superior vena cava and mild mitral and tricuspid regurgitation. G-banded karyotyping analysis showed that the pter-q11 segment of the fetal Y chromosome was connected to the Xq26 of the X chromosome, suggesting a Xq-Yq reciprocal translocation. No obvious chromosomal abnormality was found in the pregnant woman and her husband. The CMA results showed that there was approximately 21 Mb loss of heterozygosity at the end of the long arm of the fetal X chromosome [arr [hg19] Xq26.3q28(133912218_154941869)×1], and 42 Mb duplication at the end of the long arm of the Y chromosome [arr [hg19] Yq11.221qter(17405918_59032809)×1]. Combined with the search results of DGV, OMIM, DECIPHER, ClinGen and PubMed databases, and based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the deletion of arr[hg19] Xq26.3q28(133912218_154941869)×1 region was rated as pathogenic, and the duplication of arr[hg19] Yq11.221qter(17405918_59032809)×1 region was rated as variant of uncertain significance. CONCLUSION The Xq-Yq reciprocal translocation probably underlay the ultrasonographic anomalies in this fetus, and may lead to premature ovarian insufficiency and developmental delay after birth. Combined G-banded karyotyping analysis and CMA can determine the type and origin of fetal chromosomal structural abnormalities as well as distinguish balanced and unbalanced translocations, which has important reference value for the ongoing pregnancy.
Humans ; Child ; Pregnancy ; Female ; Vena Cava, Superior ; In Situ Hybridization, Fluorescence ; Chromosome Aberrations ; Karyotyping ; Translocation, Genetic ; Fetus ; Prenatal Diagnosis/methods*