A working model for the formation of Robertsonian chromosomes.

Robertsonian chromosomes form by fusion of two chromosomes that have centromeres located near their ends, known as acrocentric or telocentric chromosomes. This fusion creates a new metacentric chromosome and is a major mechanism of karyotype evolution and speciation. Robertsonian chromosomes are common in nature and were first described in grasshoppers by the zoologist W. R. B. Robertson more than 100 years ago. They have since been observed in many species, including catfish, sheep, butterflies, bats, bovids, rodents and humans, and are the most common chromosomal change in mammals. Robertsonian translocations are particularly rampant in the house mouse, Mus musculus domesticus, where they exhibit meiotic drive and create reproductive isolation. Recent progress has been made in understanding how Robertsonian chromosomes form in the human genome, highlighting some of the fundamental principles of how and why these types of fusion events occur so frequently. Consequences of these fusions include infertility and Down's syndrome. In this Hypothesis, I postulate that the conditions that allow these fusions to form are threefold: (1) sequence homology on non-homologous chromosomes, often in the form of repetitive DNA; (2) recombination initiation during meiosis; and (3) physical proximity of the homologous sequences in three-dimensional space. This Hypothesis highlights the latest progress in understanding human Robertsonian translocations within the context of the broader literature on Robertsonian chromosomes.

Optical Genome Mapping as a Potential Routine Clinical Diagnostic Method.

Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM's concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the SON gene due to a balanced reciprocal translocation; (2) disruption of the NBEA gene due to an inverted insertion; (3) disruption of the TSC2 gene due to a mosaic deletion. We show that OGM is a valid method for the detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions.

Delineating the mechanism of fragility at BCL6 breakpoint region associated with translocations in diffuse large B cell lymphoma.

BCL6 translocation is one of the most common chromosomal translocations in cancer and results in its enhanced expression in germinal center B cells. It involves the fusion of BCL6 with any of its twenty-six Ig and non-Ig translocation partners associated with diffuse large B cell lymphoma (DLBCL). Despite being discovered long back, the mechanism of BCL6 fragility is largely unknown. Analysis of the translocation breakpoints in 5' UTR of BCL6 reveals the clustering of most of the breakpoints around a region termed Cluster II. In silico analysis of the breakpoint cluster sequence identified sequence motifs that could potentially fold into non-B DNA. Results revealed that the Cluster II sequence folded into overlapping hairpin structures and identified sequences that undergo base pairing at the stem region. Further, the formation of cruciform DNA blocked DNA replication. The sodium bisulfite modification assay revealed the single-strandedness of the region corresponding to hairpin DNA in both strands of the genome. Further, we report the formation of intramolecular parallel G4 and triplex DNA, at Cluster II. Taken together, our studies reveal that multiple non-canonical DNA structures exist at the BCL6 cluster II breakpoint region and contribute to the fragility leading to BCL6 translocation in DLBCL patients.

Non-Invasive Prenatal Test Analysis Opens a Pandora's Box: Identification of Very Rare Cases of SRY-Positive Healthy Females, Segregating for Three Generations Thanks to Preferential Inactivation of the XqYp Translocated Chromosome.

The translocation of the testis-determining factor, the SRY gene, from the Y to the X chromosome is a rare event that causes abnormalities in gonadal development. In all cases of males and females carrying this translocation, disorder of sex development is reported. In our study, we described a peculiar pedigree with the first evidence of four healthy females from three generations who are carriers of the newly identified t(X;Y)(q28;p11.2)(SRY+) translocation with no evidence of ambiguous genitalia or other SRY-dependent alterations. Our study was a consequence of a Non-Invasive Prenatal Test (NIPT) showing a sexual chromosomal abnormality (XXY) followed by a chorionic villus analysis suggesting a normal karyotype 46,XX and t(X;Y) translocation detected by FISH. Here, we (i) demonstrated the inheritance of the translocation in the maternal lineage via karyotyping and FISH analysis; (ii) characterised the structural rearrangement via chromosomal microarray; and (iii) demonstrated, via Click-iT® EdU Imaging assay, that there was an absolute preferential inactivation of the der(X) chromosome responsible for the lack of SRY expression. Overall, our study provides valuable genetic and molecular information that may lead personal and medical decisions.

High-resolution PGT-A results in incidental identification of patients with small pathogenic copy number variants.

PURPOSE: This study aimed to evaluate whether a high-throughput high-resolution PGT-A method can detect copy number variants (CNVs) that could have clinical implications for patients and their embryos. METHODS: A prospective analysis of PGT-A cases was conducted using a high-resolution SNP microarray platform with over 820,000 probes. Cases where multiple embryos possessed the same segmental imbalance were identified, and preliminary PGT-A reports were issued recommending either parental microarray or conventional karyotyping to identify CNVs or translocations. RESULTS: Analysis of 6080 sequential PGT-A cases led to identification of 41 cases in which incidental findings were observed (0.7%) and parental testing was recommended. All cases, in which parental studies were completed, confirmed the original PGT-A incidental findings. In 2 of the cases, parental studies indicated a pathogenic variant with clinical implications for the associated embryos. In one of these cases, the patient was identified as a carrier of a duplication in chromosome 15q11.2:q11.2 (SNRPN + +), which is associated with autism spectrum disorder. In the second case, the patient was heterozygous positive for an interstitial deletion of 3p26.1:p26.3, which is associated with 3p deletion syndrome and had clinical implications for the patient and associated embryos. In each case, parental studies were concordant with PGT-A findings and revealed the presence of an otherwise unknown CNV. CONCLUSION: High-throughput high-resolution SNP array-based PGT-A has the ability to detect previously unknown and clinically significant parental deletions, duplications, and translocations. The use of cost-effective SNP array-based PGT-A methods may improve the effectiveness of PGT by identifying and preventing previously unknown pathogenic CNVs in children born to patients seeking in vitro fertilization.

Evaluation of genetic risk of apparently balanced chromosomal rearrangement carriers by breakpoint characterization.

PURPOSE: To report genetic characteristics and associated risk of chromosomal breaks due to chromosomal rearrangements in large samples. METHODS: MicroSeq, a technique that combines chromosome microdissection and next-generation sequencing, was used to identify chromosomal breakpoints. Long-range PCR and Sanger sequencing were used to precisely characterize 100 breakpoints in 50 ABCR carriers. RESULTS: In addition to the recurrent regions of balanced rearrangement breaks in 8q24.13, 11q11.23, and 22q11.21 that had been documented, we have discovered a 10-Mb region of 12q24.13-q24.3 that could potentially be a sparse region of balanced rearrangement breaks. We found that 898 breakpoints caused gene disruption and a total of 188 breakpoints interrupted genes recorded in OMIM. The percentage of breakpoints that disrupted autosomal dominant genes recorded in OMIM was 25.53% (48/188). Fifty-four of the precisely characterized breakpoints had 1-8-bp microhomologous sequences. CONCLUSION: Our findings provide a reference for the evaluation of the pathogenicity of mutations in related genes that cause protein truncation in clinical practice. According to the characteristics of breakpoints, non-homologous end joining and microhomology-mediated break-induced replication may be the main mechanism for ABCRs formation.

Olfactory receptor genes and chromosome 11 structural aberrations: Players or spectators?

The largest multi-gene family in metazoans is the family of olfactory receptor (OR) genes. Human ORs are organized in clusters over most chromosomes and seem to include >0.1% the human genome. Because 369 out of 856 OR genes are mapped on chromosome 11 (HSA11), we sought to determine whether they mediate structural rearrangements involving this chromosome. To this aim, we analyzed 220 specimens collected during diagnostic procedures involving structural rearrangements of chromosome 11. A total of 222 chromosomal abnormalities were included, consisting of inversions, deletions, translocations, duplications, and one insertion, detected by conventional chromosome analysis and/or fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (array-CGH). We verified by bioinformatics and statistical approaches the occurrence of breakpoints in cytobands with or without OR genes. We found that OR genes are not involved in chromosome 11 reciprocal translocations, suggesting that different DNA motifs and mechanisms based on homology or non-homology recombination can cause chromosome 11 structural alterations. We also considered the proximity between the chromosomal territories of chromosome 11 and its partner chromosomes involved in the translocations by using the deposited Hi-C data concerning the possible occurrence of chromosome interactions. Interestingly, most of the breakpoints are located in regions highly involved in chromosome interactions. Further studies should be carried out to confirm the potential role of chromosome territories' proximity in promoting genome structural variation, so fundamental in our understanding of the molecular basis of medical genetics and evolutionary genetics.

Identification of cryptic balanced translocations in couples with unexplained recurrent pregnancy loss based upon embryonic PGT-A results.

PURPOSE: The goal of this study is to determine whether any balanced translocation (BT) had been missed by previous karyotyping in patients with unexplained recurrent pregnancy loss (uRPL). METHODS: This case series included 48 uRPL-affected couples with normal karyotypes. The embryos from these couples have all undergone preimplantation testing for aneuploidies (PGT-A). Based on the PGT-A's results, 48 couples could be categorized into two groups: 17 couples whose multiple embryos were detected with similar structural variations (SVs, segmental/complete) and 31 couples without such findings but who did not develop any euploid embryo despite at least three high-quality blastocysts being tested. The peripheral blood sample of each partner was then collected for mate-pair sequencing (MPseq) to determine whether any of them were BT carriers. RESULTS: MPseq analyses identified 13 BTs in the 17 couples whose multiple embryos had similar SVs detected (13/17, 76.47%) and three BTs in the 31 couples without euploid embryo obtained (3/31, 9.7%). Among the 16 MPseq-identified BTs, six were missed due to the limited resolution of G-banding karyotyping analysis, and the rest were mostly owing to the similar banding patterns and/or comparable sizes shared by the two segments exchanged. CONCLUSION: A normal karyotype does not eliminate the possibility of carrying BT for couples with uRPL. The use of PGT-A allows us to perceive the "carrier couples" missed by karyotyping analysis, providing an increased risk of finding cryptic BTs if similar SVs are always detected on two chromosomes among multiple embryos. Nonetheless, certain carriers with translocated segments of sub-resolution may still go unnoticed.

Noncoding mutations cause super-enhancer retargeting resulting in protein synthesis dysregulation during B cell lymphoma progression.

Whole-genome sequencing of longitudinal tumor pairs representing transformation of follicular lymphoma to high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma) identified coding and noncoding genomic alterations acquired during lymphoma progression. Many of these transformation-associated alterations recurrently and focally occur at topologically associating domain resident regulatory DNA elements, including H3K4me3 promoter marks located within H3K27ac super-enhancer clusters in B cell non-Hodgkin lymphoma. One region found to undergo recurrent alteration upon transformation overlaps a super-enhancer affecting the expression of the PAX5/ZCCHC7 gene pair. ZCCHC7 encodes a subunit of the Trf4/5-Air1/2-Mtr4 polyadenylation-like complex and demonstrated copy number gain, chromosomal translocation and enhancer retargeting-mediated transcriptional upregulation upon lymphoma transformation. Consequently, lymphoma cells demonstrate nucleolar dysregulation via altered noncoding 5.8S ribosomal RNA processing. We find that a noncoding mutation acquired during lymphoma progression affects noncoding rRNA processing, thereby rewiring protein synthesis leading to oncogenic changes in the lymphoma proteome.

Secretory Carcinoma with ETV6-NTRK3 Gene Fusion and Lymph Node Metastasis in Maxillary Gingiva: A Case Report with Pathological and Molecular Correlative Studies.

Secretory carcinoma (SC), also known as mammary analogue secretory carcinoma (MASC), is a rare salivary gland neoplasm with distinctive morphology that harbors a diagnostic ETV6 gene rearrangement. MASC was first described as a type of salivary gland neoplasm in 2010 and resembles breast secretory carcinoma. It is often mistaken for other neoplasms. It usually acts as an indolent tumor but can occasionally behave in an aggressive manner. We present a rare case of a patient with an aggressive SC/MASC of maxillary gingivobuccal sulcus with microcystic, solid and papillary patterns that showed ETV6 gene rearrangement by fluorescence in situ hybridization. Next-generation sequencing revealed t(12;15)(p13;q25) ETV6-NTRK3 translocation. Because SC/MASCs harbor the ETV6-NTRK3 translocation, molecular studies and immunostains are crucial to confirm the diagnosis and direct therapy.

[CD23 positive, BCL2 rearrangement-negative germinal centre lymphomas]. / CD23-positive, BCL2-Rearrangement-negative Keimzentrumslymphome.

Acknowledgeing that the group of follicular lymphomas is to be regarded as very heterogeneous, a group of follicular lymphomas has been delineated in recent years that was characterised by an often diffuse growth (without formation of evident follicular structures) as well as expression of CD23 in the lymphoma cells and the absence of the classic BCL2 translocation. Further characteristics are a preferred inguinal localisation of the lymphomas and a localised stage with a good prognosis. Genetically, this lymphoma group is characterised by a high rate of either STAT6 or SOCS1 mutations.The ICC classification took this development into account by introducing the provisional entity CD23 positive, BCL2 rearrangement-negative germinal centre lymphoma. Further studies must now show how exactly this entity can be defined (combination of morphology, immunohistochemical phenotype, focus on genetic alterations) in order to pave the way towards a uniform classification and a better clinical characterisation of these cases - especially with regard to possible new therapeutic treatment options.

Complex Genomic Rearrangements Involving ETV6::ABL1 Gene Fusion in an Individual with Myeloid Neoplasm.

ETV6::ABL1 gene fusion is a rare recurrent genomic rearrangement associated with hematologic malignancies, and frequently occurs with additional anomalies. Due to the opposite chromosome orientations of the ETV6 and ABL1 genes, an oncogenic in-frame ETV6::ABL1 gene fusion cannot be formed by a simple translocation. The molecular mechanism of the ETV6::ABL1 fusion and the significance of co-occurring anomalies are not fully understood. We characterized genomic alterations in an individual with ETV6::ABL1 gene-fusion-positive myeloid neoplasm using various genomic technologies. Our findings uncovered a molecular mechanism of the ETV6::ABL1 fusion, in which a paracentric inversion within the short arm of chromosome 12 (12p) and a translocation between the long arm of a chromosome 9 and the 12p with the inversion were involved. In addition, we detected multiple additional anomalies in the individual, and our findings suggested that the ETV6::ABL1 fusion occurred as a secondary event in a subset of cells with the additional anomalies. We speculate that the additional anomalies may predispose to further pathogenic changes, including ETV6::ABL1 fusion, leading to neoplastic transformation.

Prenatal cfDNA Screening for Emanuel Syndrome and Other Unbalanced Products of Conception in Carriers of the Recurrent Balanced Translocation t(11;22): One Laboratory's Retrospective Experience.

Prenatal cell-free DNA screening (cfDNA) can identify fetal chromosome abnormalities beyond common trisomies. Emanuel syndrome (ES), caused by an unbalanced translocation between chromosomes 11 and 22, has lacked a reliable prenatal screening option for families with a carrier parent. A cohort of cases (n = 46) sent for cfDNA screening with indications and/or results related to ES was queried; diagnostic testing and pregnancy outcomes were requested and analyzed. No discordant results were reported or suspected; there were ten true positives with diagnostic confirmation, six likely concordant positives based on known translocations and consistent cfDNA data, and twenty-six true negatives, by diagnostic testing or birth outcomes. For cases with parental testing, all affected ES cases had maternal translocation carriers. Expanded cfDNA may provide reassurance for t(11;22) carriers with screen negative results, and screen positive results appear to reflect a likely affected fetus, especially with a known maternal translocation. Current society guidelines support the use of expanded cfDNA screening in specific circumstances, such as for translocation carriers, with appropriate counseling. Diagnostic testing is recommended for prenatal diagnosis of ES and other chromosome abnormalities in pregnancy. To our knowledge, this cohort is the largest published group of cases with prenatal screening for carriers of t(11;22).

Long-molecule scars of backup DNA repair in BRCA1- and BRCA2-deficient cancers.

Homologous recombination (HR) deficiency is associated with DNA rearrangements and cytogenetic aberrations1. Paradoxically, the types of DNA rearrangements that are specifically associated with HR-deficient cancers only minimally affect chromosomal structure2. Here, to address this apparent contradiction, we combined genome-graph analysis of short-read whole-genome sequencing (WGS) profiles across thousands of tumours with deep linked-read WGS of 46 BRCA1- or BRCA2-mutant breast cancers. These data revealed a distinct class of HR-deficiency-enriched rearrangements called reciprocal pairs. Linked-read WGS showed that reciprocal pairs with identical rearrangement orientations gave rise to one of two distinct chromosomal outcomes, distinguishable only with long-molecule data. Whereas one (cis) outcome corresponded to the copying and pasting of a small segment to a distant site, a second (trans) outcome was a quasi-balanced translocation or multi-megabase inversion with substantial (10 kb) duplications at each junction. We propose an HR-independent replication-restart repair mechanism to explain the full spectrum of reciprocal pair outcomes. Linked-read WGS also identified single-strand annealing as a repair pathway that is specific to BRCA2 deficiency in human cancers. Integrating these features in a classifier improved discrimination between BRCA1- and BRCA2-deficient genomes. In conclusion, our data reveal classes of rearrangements that are specific to BRCA1 or BRCA2 deficiency as a source of cytogenetic aberrations in HR-deficient cells.

Association between chromosome 6p21 translocation and asthenozoospermia: A retrospective, observational study.

Asthenozoospermia (AZS) is the commonest cause of male-related infertility. The patients with AZS easily exhibit infertility, with their wives having spontaneous miscarriages or seeking assisted reproductive treatment. Reciprocal chromosomal translocation (RCT) is an important chromosome structural abnormality and has been reported to affect sperm motility. Genetic counseling for male RCT patients with AZS is still a challenge. This study reported 4 RCT carriers, which were 46,XY,t(1;6) (p36.1;p21), 46,XY,t (6;10) (p21;q11.2), 46,XY,t (6;11) (p21;p15), and 46,XY,t (6;17) (p21;q21), respectively. The association between chromosome 6p21 translocation and AZS is discussed, considering 19 published cases as well. In 6 patients with available semen parameters and 4 patients in this study, all of them were diagnosed with AZS. The SLC26A8 gene and the DNAH8 gene located on chromosome 6p21 are closely related to AZS by gene search using OMIM. For the chromosome 6p21 breakpoint, 72 pathogenic genes were found through the DECIPHER search. Gene ontology analysis showed that these target genes have several molecular functions and are strongly involved in various biological processes. The proteins expressed by these genes are involved in multiple cellular components. These results suggest that the breakpoint of chromosome 6p21 in male RCT carriers is closely related to AZS. The breakpoint may disrupt the structure and function of related genes, resulting in reduced sperm motility. Karyotype analysis should be recommended for AZS patients. Chromosomes and breakpoints involved in RCT should be paid attention to in genetic counseling for patients.

Mosaicism for Robertsonian jumping translocation at amniocentesis: 45,XY,der(15;22)(q10;q10)mat/46,XY,i(15)(q10)/46,XY, genetic counseling, prenatal diagnosis and postnatal follow-up in a pregnancy with a favorable fetal outcome.

OBJECTIVE: We present genetic counseling, prenatal diagnosis and postnatal follow-up of 45,XY,der(15;22)(q10;q10)mat/46,XY,i(15)(q10)/46,XY at amniocentesis in a pregnancy with a favorable fetal outcome. CASE REPORT: A 27-year-old, primigravid woman underwent amniocentesis at 19 weeks of gestation because increased nuchal translucency thickness, and the result was 45,XY,der(15;22)(q10;q10)[29]/46,XY,i(15)(q10)[3]/46,XY[5]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (1-22) × 2, (X,Y) × 1. The maternal karyotype was 45,XX,der(15;22)(q10;q10), and the paternal karyotype was 46,XY. She was referred for genetic counseling, and repeat amniocentesis performed at 23 weeks of gestation revealed 45,XY,der(15;22)(q10;q10)mat[23]/45,XY,-22[2]. aCGH analysis on uncultured amniocytes detected no genomic imbalance, and polymorphic DNA marker analysis excluded uniparental disomy (UPD) 15. Fluorescence in situ hybridization (FISH) analysis using the chromosome 15q specific probe and the chromosome 22q specific probe detected three 15q signals in 4/104 cells (3.8%). The woman was advised to continue the pregnancy, and, a 3186-g phenotypically normal male baby was delivered at 38 weeks of gestation. The umbilical cord had a karyotype of 45,XY,der(15;22)(q10;q10) (40/40 cells). When follow-up at age seven months, the neonate was normal in development, the peripheral blood had a karyotype of 45,XY,der(15;22)(q10;q10) (40/40 cells), and the buccal mucosal cells had normal signals in all 100 cells. CONCLUSIONS: Mosaicism for Robertsonian jumping translocations at amniocentesis can be a transient condition and can be associated with a familial Robertsonian translocation and a favorable fetal outcome. Prenatal diagnosis of a Robertsonian jumping translocation involving chromosome 15 should include UPD 15 testing to exclude UPD 15.

Multiplex Editing of the Nucleoredoxin1 Tandem Array in Poplar: From Small Indels to Translocations and Complex Inversions.

The CRISPR-Cas9 system has been deployed for precision mutagenesis in an ever-growing number of species, including agricultural crops and forest trees. Its application to closely linked genes with extremely high sequence similarities has been less explored. In this study, we used CRISPR-Cas9 to mutagenize a tandem array of seven Nucleoredoxin1 (NRX1) genes spanning ∼100 kb in Populus tremula × Populus alba. We demonstrated efficient multiplex editing with one single guide RNA in 42 transgenic lines. The mutation profiles ranged from small insertions and deletions and local deletions in individual genes to large genomic dropouts and rearrangements spanning tandem genes. We also detected complex rearrangements including translocations and inversions resulting from multiple cleavage and repair events. Target capture sequencing was instrumental for unbiased assessments of repair outcomes to reconstruct unusual mutant alleles. The work highlights the power of CRISPR-Cas9 for multiplex editing of tandemly duplicated genes to generate diverse mutants with structural and copy number variations to aid future functional characterization.

Chromosome translocation affects multiple phenotypes, causes genome-wide dysregulation of gene expression, and remodels metabolome in hexaploid wheat.

Chromosomal rearrangements (CRs) may occur in newly formed polyploids due to compromised meiotic fidelity. Moreover, CRs can be more readily tolerated in polyploids allowing their longer-term retention and hence potential spreading/fixation within a lineage. The direct functional consequences of CRs in plant polyploids remain unexplored. Here, we identified a heterozygous individual from a synthetic allohexaploid wheat in which the terminal parts of the long-arms of chromosomes 2D (approximately 193 Mb) and 4A (approximately 167 Mb) were reciprocally translocated. Five homogeneous translocation lines including both unbalanced and balanced types were developed by selfing fertilization of the founder mutant (RT [2DL; 4AL]-ter/1, reciprocal translocation). We investigated impacts of these translocations on phenotype, genome-wide gene expression and metabolome. We find that, compared with sibling wild-type, CRs in the form of both unbalanced and balanced translocations induced substantial changes of gene expression primarily via trans-regulation in the nascent allopolyploid wheat. The CRs also manifested clear phenotypic and metabolic consequences. In particular, the genetically balanced, stable reciprocal translocations lines showed immediate enhanced reproductive fitness relative to wild type. Our results underscore the profound impact of CRs on gene expression in nascent allopolyploids with wide-ranging phenotypic and metabolic consequences, suggesting CRs are an important source of genetic variation that can be exploited for crop breeding.

The effect of carrier characteristics and female age on preimplantation genetic testing results of blastocysts from Robertsonian translocation carriers.

PURPOSE: To analyze factors affecting segregation and ploidy results from Robertsonian carriers, and determine chromosomes involved impact chromosome stability during meiosis and mitosis. METHODS: This retrospective study include 928 oocyte retrieval cycles from 763 couples with Robertsonian translocations undergoing preimplantation genetic testing for structural rearrangements (PGT-SR) using next-generation sequencing (NGS) between December 2012 and June 2020.The segregation patterns of the trivalent of 3423 blastocysts were analyzed according to the carrier's sex and age. A total of 1492 couples who received preimplantation genetic testing for aneuploidy (PGT-A) were included as the control group and matched according to maternal age and testing time stage. RESULTS: A total of 1728 (50.5%) normal/balanced embryos were identified from 3423 embryos diagnosed. The rate of alternate segregation in male Robertsonian translocation carriers was significantly higher than that in female carriers (82.3% vs. 60.0%, P < 0.001). However, the segregation ratio exhibited no difference between young and older carriers. Further, increasing maternal age decreased the proportion of transferable embryo cycle in both female and male carriers. And the ratio of chromosome mosaic from the Robertsonian translocation carrier group was significantly higher than that in the PGT-A control group (1.2% vs. 0.5%, P < 0.01). CONCLUSIONS: The meiotic segregation modes were affected by the carrier sex and were independent of the carrier's age. Advanced maternal age decreased the probability of obtaining a normal/balanced embryo. In additional, the Robertsonian translocation chromosome could increase the possibility of chromosome mosaicism during mitosis in blastocysts.