3q29 duplications: A cohort of 46 patients and a literature review.

Duplications of the 3q29 cytoband are rare chromosomal copy number variations (CNVs) (overlapping or recurrent ~1.6 Mb 3q29 duplications). They have been associated with highly variable neurodevelopmental disorders (NDDs) with various associated features or reported as a susceptibility factor to the development of learning disabilities and neuropsychiatric disorders. The smallest region of overlap and the phenotype of 3q29 duplications remain uncertain. We here report a French cohort of 31 families with a 3q29 duplication identified by chromosomal microarray analysis (CMA), including 14 recurrent 1.6 Mb duplications, eight overlapping duplications (>1 Mb), and nine small duplications (<1 Mb). Additional genetic findings that may be involved in the phenotype were identified in 11 patients. Focusing on apparently isolated 3q29 duplications, patients present mainly mild NDD as suggested by a high rate of learning disabilities in contrast to a low proportion of patients with intellectual disabilities. Although some are de novo, most of the 3q29 duplications are inherited from a parent with a similar mild phenotype. Besides, the study of small 3q29 duplications does not provide evidence for any critical region. Our data suggest that the overlapping and recurrent 3q29 duplications seem to lead to mild NDD and that a severe or syndromic clinical presentation should warrant further genetic analyses.

Does the prognosis after PGT for structural rearrangement differ between female and male translocation carriers?

RESEARCH QUESTION: Chromosomal translocations are known genetic causes of premature ovarian insufficiency syndrome. Are certain translocations associated with decreased capacity of small antral follicles to respond to exogenous FSH? Does the prognosis after preimplantation genetic testing for structural rearrangements differ in couples with female or male translocation carriers and according to the type of translocation? DESIGN: A single-centre, retrospective, observational study covering a 10-year period. One hundred and thirty-nine females carrying a translocation were compared with 192 partners of male translocation carriers. To evaluate ovarian response to FSH, the follicular output rate was used, defined by ratio between the pre-ovulatory follicle count on day of HCG x 100/antral follicle count (AFC). To determine a cut-off of metaphase II oocytes and biopsied embryos as predictor of obtaining a balanced embryo transfer, receiver operator characteristic curves were plotted. RESULT: A decreased capacity of small antral follicles to respond to exogenous FSH in female translocation carriers was found. The number of metaphase II oocytes in both groups was weakly informative as a predictor of obtaining an embryo transfer. The number of biopsied embryos had some clinical value, however, and allowed a cut-off of 6.5 to be determined for female translocation carriers versus 5.5 for the partners of male translocation carriers. Live birth rates, however, were not different between female and male translocations carriers. CONCLUSIONS: Female translocation carriers may respond poorly to ovarian stimulation, and present a higher rate of unbalanced embryos, which means that higher gonadotrophin doses may be required to increase the number of biopsied embryos.

De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome.

The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development.

Chromosomal translocations and semen quality: A study on 144 male translocation carriers.

RESEARCH QUESTION: Chromosomal translocations are known genetic causes of male infertility. Are certain translocations or chromosomal regions more directly associated with sperm defects? Is there a threshold of sperm impairment that can be relevant for detection of translocations? DESIGN: This is a monocentric retrospective observational study covering a 10-year period. Eighty-one patients carrying a reciprocal translocation (RCT) and 63 carrying a Robertsonian translocation (ROBT) were compared with 105 fertile patients. Semen quality before and after sperm migration was compared. The aims were to define whether a threshold based on sperm analysis could be proposed for detection of translocations and to identify whether some redundant chromosomal regions might be associated with sperm quality defects. RESULTS: The number of progressive spermatozoa retrieved after sperm preparation (NPS-ASP) was altered in both RCT and ROBT carriers compared with controls, with a stronger alteration in ROBT. Based on the NPS-ASP results in this large group of translocation carriers, a relatively robust threshold, fixed at less than 5 million, may be proposed for detection of translocations. The alteration of NPS-ASP was independent of the chromosome involved in ROBT, while in RCT, four redundant chromosomal regions (1q21, 6p21, 16q21, 17q11.2) were associated with poor or very poor NPS-ASP. CONCLUSIONS: The NPS-ASP appears to be a good parameter to assess sperm function and would be a useful tool to detect chromosomal translocations. Four redundant regions have been identified on four chromosomes, suggesting that they may contain genes of interest to study sperm functions.

Array-CGH predicts prognosis in plasma cell post-transplantation lymphoproliferative disorders.

Plasma-cell post-transplantation lymphoproliferative disorder (PC-PTLD) is a rare monomorphic PTLD entity divided into plasma cell myeloma (PCM) and plasmacytoma-like lesion (PLL) PTLD. To date, there are no exhaustive published cytogenetic data on PC-PTLD. We report array-based comparative genomic hybridization (aCGH) of 10 cases of PCM and PLL-PTLD. Patients had received kidney (n = 6), heart (n = 2), lung (n = 1) or bone marrow (n = 1) transplantation. There were six men and median age at time of PTLD was 56.5 years (3-74). We identified two different cytological features, plasmacytic and plasmablastic, among six PLL and three PCM PTLD. Eight cases were associated with EBV. First line treatment was heterogeneous: rituximab alone (n = 5), CHOP-like (n = 3) and multiple myeloma-like (n = 1). One patient died before any treatment. After a median follow-up of 19.5 months (0-150), five patients died (four from PTLD) and five were alive without evidence of disease. By aCGH, 5/10 demonstrated a complex profile. The most frequent abnormalities were +7q (5/10), +16q (5/10), +17q (5/10), +17p (4/10), +5q (4/10), t7 (4/10), t9 (3/10), del1p (3/10). No del17p13 (TP53) were observed. Del1p32.3 (CDKN2C) was observed in 2 cases. On univariate prognostic analysis, a complex aCGH was associated with a shorter OS. Thus, cytogenetic abnormalities seem to be closely related to those reported in multiple myeloma or diffuse large B cell lymphoma. Complex aCGH constitutes an unfavorable prognostic marker and aCGH should be integrated in the evaluation of patients with PLL/PCM-PTLD. © 2016 Wiley Periodicals, Inc.

Formation of Nup98-containing nuclear bodies in HeLa sublines is linked to genomic rearrangements affecting chromosome 11.

Nup98 is an important component of the nuclear pore complex (NPC) and also a rare but recurrent target for chromosomal translocation in leukaemogenesis. Nup98 contains multiple cohesive Gly-Leu-Phe-Gly (GLFG) repeats that are critical notably for the formation of intranuclear GLFG bodies. Previous studies have reported the existence of GLFG bodies in cells overexpressing exogenous Nup98 or in a HeLa subline (HeLa-C) expressing an unusual elevated amount of endogenous Nup98. Here, we have analysed the presence of Nup98-containing bodies in several human cell lines. We found that HEp-2, another HeLa subline, contains GLFG bodies that are distinct from those identified in HeLa-C. Rapid amplification of cDNA ends (RACE) revealed that HEp-2 cells express additional truncated forms of Nup98 fused to a non-coding region of chromosome 11q22.1. Cytogenetic analyses using FISH and array-CGH further revealed chromosomal rearrangements that were distinct from those observed in leukaemic cells. Indeed, HEp-2 cells feature a massive amplification of juxtaposed NUP98 and 11q22.1 loci on a chromosome marker derived from chromosome 3. Unexpectedly, minor co-amplifications of NUP98 and 11q22.1 loci were also observed in other HeLa sublines, but on rearranged chromosomes 11. Altogether, this study reveals that distinct genomic rearrangements affecting NUP98 are associated with the formation of GLFG bodies in specific HeLa sublines.

First fetal case of the 8q24.3 contiguous genes syndrome.

Molecular cytogenetics, particularly array-CGH, opened the way to the « genotype first approach ¼ and for the discovery of new micro rearrangement syndromes. This was the case for the 8q24.3 microdeletion syndrome. Here, we describe the phenotype of a fetus with a 8q24.3 deletion. This rare condition has to be considered as a contiguous genes syndrome because its phenotype is generated by the SCRIB and PUF60 adjacent gene endophenotypes. The fetus presented atrioventricular septal defect and hypoplastic aortic arch, facial dysmorphism, microretrognathia, dysmorphic ears, clinodactyly of the 5th digit on both hands, mild rocker bottom feet and abnormal third sacral vertebra. This fetus is the first case where the endophenotype produced by SCRIB gene is absent. This case is compared with the previous published cases.

Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection.

BACKGROUND: Exophiala species are mostly responsible for skin infections. Invasive Exophiala dermatitidis disease is a rare and frequently fatal infection, with 42 cases reported. About half of these cases had no known risk factors. Similarly, invasive Exophiala spinifera disease is extremely rare, with only 3 cases reported, all in patients with no known immunodeficiency. Autosomal recessive CARD9 deficiency has recently been reported in otherwise healthy patients with severe fungal diseases caused by Candida species, dermatophytes, or Phialophora verrucosa. METHODS: We investigated an 8-year-old girl from a nonconsanguineous Angolan kindred, who was born in France and developed disseminated E. dermatitidis disease and a 26 year-old woman from an Iranian consaguineous kindred, who was living in Iran and developed disseminated E. spinifera disease. Both patients were otherwise healthy. RESULTS: We sequenced CARD9 and found both patients to be homozygous for loss-of-function mutations (R18W and E323del). The first patient had segmental uniparental disomy of chromosome 9, carrying 2 copies of the maternal CARD9 mutated allele. CONCLUSIONS: These are the first 2 patients with inherited CARD9 deficiency and invasive Exophiala disease to be described. CARD9 deficiency should thus be considered in patients with unexplained invasive Exophiala species disease, even in the absence of other infections.

A French Approach to Test Fetuses with Ultrasound Abnormalities Using a Customized Microarray as First-Tier Genetic Test.

Cytogenetic microarray analysis is now the first-tier genetic test used in a postnatal clinical setting to explore genomic imbalances in individuals with developmental disability and/or birth defects. However, in a prenatal setting, this technique is not widely implemented, largely because the clinical impact of some copy number variants (CNVs) remains difficult to assess. This limitation is especially true in France where termination of pregnancy for medical reasons may be performed at any stage of gestation. During a period of 15 months, we investigated 382 fetuses presenting with ultrasound anomalies, using a customized microarray designed to avoid the detection of CNVs raising challenges for genetic counseling. After excluding common aneuploidies, 20/374 (5.3%) fetuses had a pathogenic CNV, among which 12/374 (3.2%) could have been detected by karyotyping, whereas 8/374 (2.1%) were cryptic. Within these 374 cases, 300 were ongoing pregnancies at the time of array comparative genomic hybridization (aCGH) testing. For these pregnancies, we detected 18/300 (6%) pathogenic CNVs, among which 6/300 (2%) were cryptic. Using this approach, only 2/300 (0.6%) of the detected CNVs raised difficulties for genetic counseling. This study confirms the added value of this strategy in a prenatal clinical setting to minimize ethical issues for genetic counseling while enhancing the detection of genomic imbalances.

Phenotype-genotype correlations in 17 new patients with an Xp11.23p11.22 microduplication and review of the literature.

Array comparative genomic hybridization (array CGH) has proven its utility in uncovering cryptic rearrangements in patients with X-linked intellectual disability. In 2009, Giorda et al. identified inherited and de novo recurrent Xp11.23p11.22 microduplications in two males and six females from a wide cohort of patients presenting with syndromic intellectual disability. To date, 14 females and 5 males with an overlapping microduplication have been reported in the literature. To further characterize this emerging syndrome, we collected clinical and microarray data from 17 new patients, 10 females, and 7 males. The Xp11.23p11.2 microduplications detected by array CGH ranged in size from 331 Kb to 8.9 Mb. Five patients harbored 4.5 Mb recurrent duplications mediated by non-allelic homologous recombination between segmental duplications and 12 harbored atypical duplications. The chromosomal rearrangement occurred de novo in eight patients and was inherited in six affected males from three families. Patients shared several common major characteristics including moderate to severe intellectual disability, early onset of puberty, language impairment, and age related epileptic syndromes such as West syndrome and focal epilepsy with activation during sleep evolving in some patients to continuous spikes-and-waves during slow sleep. Atypical microduplications allowed us to identify minimal critical regions that might be responsible for specific clinical findings of the syndrome and to suggest possible candidate genes: FTSJ1 and SHROOM4 for intellectual disability along with PQBP1 and SLC35A2 for epilepsy. Xp11.23p11.22 microduplication is a recently-recognized syndrome associated with intellectual disability, epilepsy, and early onset of puberty in females. In this study, we propose several genes that could contribute to the phenotype.

Extensive molecular mapping of TCRα/δ- and TCRß-involved chromosomal translocations reveals distinct mechanisms of oncogene activation in T-ALL.

Chromosomal translocations involving the TCR loci represent one of the most recurrent oncogenic hallmarks of T-cell acute lymphoblastic leukemia (T-ALL) and are generally believed to result from illegitimate V(D)J recombination events. However, molecular characterization and evaluation of the extent of recombinase involvement at the TCR-oncogene junction has not been fully evaluated. In the present study, screening for TCRß and TCRα/δ translocations by FISH and ligation-mediated PCR in 280 T-ALLs allowed the identification of 4 previously unreported TCR-translocated oncogene partners: GNAG, LEF1, NKX2-4, and IL2RB. Molecular mapping of genomic junctions from TCR translocations showed that the majority of oncogenic partner breakpoints are not recombinase mediated and that the regulatory elements predominantly used to drive oncogene expression differ markedly in TCRß (which are exclusively enhancer driven) and TCRα/δ (which use an enhancer-independent cryptic internal promoter) translocations. Our data also imply that oncogene activation takes place at a very immature stage of thymic development, when Dδ2-Dδ3/Dδ3-Jδ1 and Dß-Jß rearrangements occur, whereas the bulk leukemic maturation arrest occurs at a much later (cortical) stage. These observations have implications for T-ALL therapy, because the preleukemic early thymic clonogenic population needs to be eradicated and its disappearance monitored.

Multiple congenital anomalies-intellectual disability (MCA-ID) and neuroblastoma in a patient harboring a de novo 14q23.1q23.3 deletion.

Neuroblastoma is the most frequent extra cranial solid tumor in infants and children. Genetic predisposition to neuroblastoma has been suspected previously due to familial cases of sporadic NB and predisposition to NB in several syndromes. Here, we report on a de novo 14q23.1-q23.3 microdeletion in a male presenting with a neuroblastoma diagnosed at 9 months, and spherocytosis, congenital heart defect, cryptorchidism, hypoplasia of corpus callosum, epilepsy, and developmental delay. Myc-associated-factor X (MAX) haploinsufficiency could be regarded as the predisposing factor to NB. Indeed 14q deletion is a recurrent somatic rearrangement in NB and MAX somatic and germline loss of function mutation have recently been described in pheochromocytoma and paraganglioma. However, MAX was expressed in the tumor of the patient we report on and, accordingly, loss of heterozygosity, mutation, or promoter methylation were excluded. In addition, we discuss the potential involvement in the clinical spectrum presented by the patient of five of the deleted genes, namely DAAM1, PLEKHG3, SPTB, AKAP5, and ARID4A.

Enteropathy-associated T-cell lymphoma complicating an autoimmune enteropathy.

Enteropathy-associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma frequently associated with celiac disease. We report a case of EATL complicating adult autoimmune enteropathy (AIE). Analysis of phenotype, rearrangements in T-cell receptor genes, and chromosome alterations by high-resolution comparative genomic hybridization identified features distinct from those described for types I and II EATL. Furthermore, EATL arose from a single T-cell clone that had been present for several years in AIE-associated, oligoclonal, intestinal T-cell infiltrate. Emerging T-cell clones should be monitored in patients with AIE who receive long-term immunosuppressive therapy.

Loss of p19Arf in a Rag1(-/-) B-cell precursor population initiates acute B-lymphoblastic leukemia.

In human B-acute lymphoblastic leukemia (B-ALL), RAG1-induced genomic alterations are important for disease progression. However, given that biallelic loss of the RAG1 locus is observed in a subset of cases, RAG1's role in the development of B-ALL remains unclear. We chose a p19Arf(-/-)Rag1(-/-) mouse model to confirm the previously published results concerning the contribution of CDKN2A (p19ARF /INK4a) and RAG1 copy number alterations in precursor B cells to the initiation and/or progression to B-acute lymphoblastic leukemia (B-ALL). In this murine model, we identified a new, Rag1-independent leukemia-initiating mechanism originating from a Sca1(+)CD19(+) precursor cell population and showed that Notch1 expression accelerates the cells' self-renewal capacity in vitro. In human RAG1-deficient BM, a similar CD34(+)CD19(+) population expressed p19ARF. These findings suggest that combined loss of p19Arf and Rag1 results in B-cell precursor leukemia in mice and may contribute to the progression of precursor B-ALL in humans.

Mutation in TET2 in myeloid cancers.

BACKGROUND: The myelodysplastic syndromes and myeloproliferative disorders are associated with deregulated production of myeloid cells. The mechanisms underlying these disorders are not well defined. METHODS: We conducted a combination of molecular, cytogenetic, comparative-genomic-hybridization, and single-nucleotide-polymorphism analyses to identify a candidate tumor-suppressor gene common to patients with myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia (AML). The coding sequence of this gene, TET2, was determined in 320 patients. We analyzed the consequences of deletions or mutations in TET2 with the use of in vitro clonal assays and transplantation of human tumor cells into mice. RESULTS: We initially identified deletions or mutations in TET2 in three patients with myelodysplastic syndromes, in three of five patients with myeloproliferative disorders, in two patients with primary AML, and in one patient with secondary AML. We selected the six patients with myelodysplastic syndromes or AML because they carried acquired rearrangements on chromosome 4q24; we selected the five patients with myeloproliferative disorders because they carried a dominant clone in hematopoietic progenitor cells that was positive for the V617F mutation in the Janus kinase 2 (JAK2) gene. TET2 defects were observed in 15 of 81 patients with myelodysplastic syndromes (19%), in 24 of 198 patients with myeloproliferative disorders (12%) (with or without the JAK2 V617F mutation), in 5 of 21 patients with secondary AML (24%), and in 2 of 9 patients with chronic myelomonocytic leukemia (22%). TET2 defects were present in hematopoietic stem cells and preceded the JAK2 V617F mutation in the five samples from patients with myeloproliferative disorders that we analyzed. CONCLUSIONS: Somatic mutations in TET2 occur in about 15% of patients with various myeloid cancers.

NUP98-MLL fusion in human acute myeloblastic leukemia.

Posttranscriptional modifications of histones play important roles in the control of chromatin structure and transcription. H3K4 (histone H3 lysine 4) methylation by the SET domain of the trithorax-group protein MLL (mixed-lineage leukemia) is important for the control of homeobox (HOX) gene expression during development. MLL is tethered to the HOXA locus through interaction of its amino-terminus with menin. MLL fusion proteins associated with human leukemia contain the menin interaction peptide and frequently recruit H3K79 (histone H3 lysine 79) methylation activity. This allows sustained expression of HOXA genes important for cellular transformation. We have characterized a novel recurrent chromosomal aberration, inv(11)(p15q23), as an isolated chromosomal abnormality in 2 patients with acute myeloid leukemia. This aberration is predicted to result in the expression of an NUP98 (nucleoporin 98 kDa)-MLL fusion protein that is unable to interact with menin. As expected, low levels of HOXA gene expression were observed in the patients' samples. This fusion protein is predicted to participate in cellular transformation by activating MLL targets other than HOXA genes.

Functional analysis of the NUP98-CCDC28A fusion protein.

BACKGROUND: The nucleoporin gene NUP98 is rearranged in more than 27 chromosomal abnormalities observed in childhood and adult, de novo and therapy-related acute leukemias of myeloid and T-lymphoid origins, resulting in the creation of fusion genes and the expression of chimeric proteins. We report here the functional analysis of the NUP98-coiled-coil domain-containing protein 28A (NUP98-CCDC28A) fusion protein, expressed as the consequence of a recurrent t(6;11)(q24.1;p15.5) translocation. DESIGN AND METHODS: To gain insight into the function of the native CCDC28A gene, we collected information on any differential expression of CCDC28A among normal hematologic cell types and within subgroups of acute leukemia. To assess the in vivo effects of the NUP98-CCDC28A fusion, NUP98-CCDC28A or full length CCDC28A were retrovirally transduced into primary murine bone marrow cells and transduced cells were next transplanted into sub-lethally irradiated recipient mice. RESULTS: Our in silico analyses supported a contribution of CCDC28A to discrete stages of murine hematopoietic development. They also suggested selective enrichment of CCDC28A in the French-American-British M6 class of human acute leukemia. Primary murine hematopoietic progenitor cells transduced with NUP98-CCDC28A generated a fully penetrant and transplantable myeloproliferative neoplasm-like myeloid leukemia and induced selective expansion of granulocyte/macrophage progenitors in the bone marrow of transplanted recipients, showing that NUP98-CCDC28A promotes the proliferative capacity and self-renewal potential of myeloid progenitors. In addition, the transformation mediated by NUP98-CCDC28A was not associated with deregulation of the Hoxa-Meis1 pathway, a feature shared by a diverse set of NUP98 fusions. CONCLUSIONS: Our results demonstrate that the recurrent NUP98-CCDC28A is an oncogene that induces a rapid and transplantable myeloid neoplasm in recipient mice. They also provide additional evidence for an alternative leukemogenic mechanism for NUP98 oncogenes.

Second biopsy for embryos with inconclusive results after preimplantation genetic testing: Impact on pregnancy outcomes.

In this study, we aimed to evaluate the pregnancy outcomes for embryos biopsied twice at cleavage and blastocyst stage for preimplantation genetic testing (PGT). This retrospective monocentric study, conducted between January 2016 and March 2021, described all PGT results on one hand and the PGT results for undiagnosed embryos submitted to a second biopsy on the other hand. Among the 5865 embryos biopsied during the study period, 510 embryos were genetic undiagnosed after the first embryo biopsy at cleavage stage (8.7%). The rate of undiagnosed embryos was significantly higher for PGT for structural rearrangement (PGT-SR) than PGT for monogenic disease (PGT-M) (10.2% vs 7.4% respectively, p < 0.001). Thirty-three embryos were compatible with a second biopsy at blastocyst stage before being directly frozen. Among them 17 were diagnosed as healthy for the researched pathology (51.5%). At the time of our study, 11 of the 17 preserved embryos were thawed and transferred. Embryo survival at thawing was 100% and 5 pregnancies were obtained (clinical pregnancy rate of 45.5% per transfer), including 3 live births. A second biopsy for inconclusive embryos after PGT does not seem to have an impact on thaw survival and implantation rate. For couple, this strategy avoids to discard transferable embryos.

A fertilin-derived peptide improves in vitro maturation and ploidy of human oocytes.

OBJECTIVE: To analyze the effect of a cyclic fertilin-derived peptide (cFEE) on in vitro maturation of human oocytes. DESIGN: Randomized study. SETTING: Fertility center in an academic hospital. PATIENT(S): Not applicable. INTERVENTION(S): Human immature germinal vesicle-stage oocytes (n = 1,629) donated for research according to French bioethics laws were randomly allocated to groups treated with 1 or 100 µM of cFEE or to a control group. They were incubated at 37 °C in 6% CO2 and 5% O2, and their maturation was assessed using time-lapse microscopy over 24 hours. In vitro maturated metaphase II oocytes were analyzed for chromosomal content using microarray comparative genomic hybridization, and their transcriptomes were analyzed using Affymetrix Clariom D microarrays. MAIN OUTCOME MEASURE(S): The percentage of oocytes undergoing maturation in vitro was observed. Aneuploidy and euploidy were assessed for all chromosomes, and differential gene expression was analyzed in oocytes treated with cFEE compared with the control to obtain insights into its mechanism of action. RESULT(S): cFEE significantly increased the percentage of oocytes that matured in vitro and improved euploidy in meiosis II oocytes by the up-regulation of FMN1 and FLNA genes, both of which encode proteins involved in spindle structure. CONCLUSION(S): cFEE improves human oocyte maturation in vitro and reduces aneuploidy. It may prove useful for treating oocytes before fertilization in assisted reproductive technology and for in vitro maturation in fertility preservation programs to improve oocyte quality and the chances for infertile couples to conceive.