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Objective: We described a unique case of near-negative chromosome mosaicism in chorionic villi but complete monosomy X in amniotic fluid. Methods: Chorionic villus sampling and amniocentesis were performed separately in the first and second trimesters. Chromosomal microarray (CMA) and rapid aneuploidy detection (QF-PCR and FISH) were performed on placental villi and uncultured amniotic fluid. After pregnancy termination, the placenta, umbilical cord, and fetal muscle tissues were sampled for FISH detection. Results: The CMA revealed a lower signal from chromosome X in chorionic villi, with a copy number of 1.85, implying the presence of mosaic monosomy X. However, the QF-PCR and FISH results were nearly normal. In uncultured amniotic fluid, CMA and rapid aneuploidy detection indicated complete monosomy X. Across different sampling points on the aborted fetus, the FISH results varied from normal, to mosaic, and then complete monosomy X. Conclusion: This case presents a rare and complex situation where sampling from uncultured chorionic villi indicated low-level chromosome mosaicism, while sampling from amniotic fluid revealed complete monosomy X. Although some of these discordant outcomes may be due to methodological limitations, we conclude that prenatal consultation should be combined with fetal ultrasound phenotype and genetic testing for a comprehensive evaluation of fetal genetic abnormalities. [ABSTRACT FROM AUTHOR]

Objective·To analyze the clinical features of the patients with 45, X/46, XY mosaicism, and improve the understanding, diagnosis and treatment of the disease. Methods·The clinical manifestations, the level of sex hormones, and the gonads pathology of the patients with 45,X/46,XY mosaicism diagnosed by G-banding karyotype analysis and fluorescence in situ hybridization (FISH) were retrospectively analyzed, who were admitted in Children's Hospital of Soochow University from January 2014 to December 2020. Results·Twenty-three patients with 45,X/46,XY mosaicism were included, among whom 11 cases were the female phenotype, and 12 cases were the male phenotype. In these patients, 12 patients were diagnosed by Gbanding karyotype analysis, 10 patients were diagnosed by FISH, and only 1 patient was diagnosed by array-based comparative genomic hybridization. The age of the first diagnosis was 0.3-14.9 years. The mean age of the patients with the female phenotype was (9.3±3.9) years, which was bigger than that of the male phenotype [(4.4±3.7) years, P<0.05]. All the patients above 1 year old had different degrees of short stature, especially in the female phenotype patients. In the female phenotype patients, three patients had clitoromegaly, while the other patients had no masculine appearance of external genitalia. The external masculinisation scores (EMS) of the patients with the female phenotype were 0-2.5. Twelve patients with the male phenotype were in pre-adolescent state, among whom 4 patients had hypospadias combined with cryptorchidism, 3 patients had hypospadias, 3 patients had small testicles, and 2 patients had normal external genitalia. The EMS of them ranged from 4 to 12, with a mean score of 10.5. All the patients with the female phenotype had hypergonadotropic hypogonadism, while most of the patients with the male phenotype had gonadotropin levels matched with their age. There were 3 patients with the female phenotype having gonadoblastomas. Conclusion·The 45,X/46,XY mosaicism patients present a wide spectrum of manifestations. The risk of gonadal malignancy onset should be emphasized. EMS has guiding significance for clinical evaluation of these patients. [ABSTRACT FROM AUTHOR]

No more than 10—20% of children with autism, as becoming adults can adapt to a relatively independent life. Despite many publications dedicated to autism, relatively little work has examined the output characteristics and pathomorphosis of psychic and cognitive disorders in people with autism spectrum disorders (ASD). Only few longitudinal studies allow us to represent what happens in later life with people who have ASD. For conducting effective correctional interventions overcomingwith children with ASD there is need to identify predictors of successful overcome of disorders. The basis for the study, conducted by a team of psychologists and neuroscientists, was the assumption that the information about the features of violations of basic neurobiological mechanisms in people with autism spectrum disorders should determine the tactics of assistance. Genetic, neurophysiological and psychological factors, causing more successful overcoming of these disorders in children are revealed.

Background: Chromosomal mosaicism is observed as the presence of both euploid and aneuploid cells in a particular blastocyst. Recent studies have reported that the implantation rate of mosaic embryo transfer is remarkably lower than the euploid embryos. The superior capability of next-generation sequencing (NGS) to detect chromosomal mosaicism in preimplantation genetic screening (PGS) remains controversial, and several data displayed similar implantation and pregnancy rates using NGS or array comparative genomic hybridization (aCGH). Results: In this study, the main inconsistency of aneuploidy detection and clinical performance between the NGS and aCGH were assessed. The phase I consisted of a parallel comparison in 182 blastocysts from 45 selected PGS patients for both the NGS and aCGH platforms. The phase II retrospectively compared the clinical outcomes of 90 patients with NGSscreened euploid embryo transfer to that of 129 patients with aCGH-screened euploid embryo transfer. The parallel comparison showed that the inconsistency of embryo euploidy was 11.8% (p = 0.01). Chromosomal mosaicism (10.7% with NGS vs. 3.9% with aCGH) and segmental aneuploidy (10.7% with NGS vs. 6.7% with aCGH) contributed to the discrepancy mainly. The chromosomally mosaic embryos (20%-50% of aneuploidy) and several embryos with segmental aneuploidy (≥10 Mbp) were hard to distinguish using the aCGH platform, but could be clearly identified using the NGS platform. After the first euploid embryo cryotransfer, the β-HCG(+) rate and implantation rate significantly increased in the PGS/NGS patients (HCG[+] rate: 73.3% in PGS/NGS vs. 60.5% in PGS/aCGH, p = 0.048; implantation rate: 53.2% in PGS/NGS vs. 45.0% in PGS/aCGH, p = 0.043). The clinical and ongoing pregnancy rates appeared higher in the NGS group, but did not reached statistical significance. Conclusions: The results demonstrated that the NGS platform can identify embryos with chromosomal mosaicism and segmental aneuploidy more precisely than the aCGH platform, and the following clinical performance of NGS was more favorable. [ABSTRACT FROM AUTHOR]

One of the colchicine treated plants of the cultivar Co of Capsicum annuum L. was found to be a chromosome mosaic without seed-set and with as low as 4·95% pollen fertility. The growth of the plant was stunted. Its chromosome number (2n) varied from 38 to 96. Chromosome associations and chiasma frequencies were studied in each of the chromosome classes. Bivalents and association of 4 chromosomes were prevalent. Univalents were common. Laggards were observed at anaphases I and II. The chromosome mosaicism is attributed to the effect of colchicine on the spindle and physiological process. [ABSTRACT FROM AUTHOR]

A 2-month-old female infant with typical features of the 13q- syndrome was found to be a hitherto unreported mosaic consisting of 46,XX,del (13)(q22)/46,XX,r(13)(p13q22). She has not been able to maintain normal values of serum Na and Cl since the second day of life: this may be induced by cerebral dysgenesis. [ABSTRACT FROM AUTHOR]

We studied a patient with a sporadic mental retardation/multiple congenital anomalies syndrome. Chromosome analysis showed a 46,XX, inv(9)( p11; q13) karyotype in all lymphocytes. Fibroblasts from two separate skin biopsies revealed a mosaic karyotype. Some 22.5% of fibroblasts had a karyotype like that of the lymphocytes, while 77.5% of fibroblasts had a karyotype 46,XX,inv(9)( p11; q13),der(12), t(12;?)( p13;?). The data in this case emphasize the drawbacks of confining cytogenetic analysis to lymphocytes. [ABSTRACT FROM AUTHOR]

The chromosomal status of calli and plantlets regenerated from Pisum sativum shoot apical meristems was studied. Chromosome mosaicism (aneusomaty) occurs during callus induction and proliferation, mostly owing to nuclear fragmentation prior to mitosis in the first days of culture. Plantlets regenerated from calli are diploid or aneusomatic, but a selective advantage of diploid cells (diplontic selection) takes place with plantlet growth. The results are discussed in relation to the possibility of inducing chromosomal and/or genetic variability by using meristematic tissues as expiants. [ABSTRACT FROM AUTHOR]

Bellevalia romana (L.) Rchb., a monocotyledonous plant characterized by few (2 n=2 x=8) and very large chromosomes, is a useful subject for studying developmental problems in vitro. Cytological analysis of callus revealed that the majority of cells were diploid, but the remaining cells had aneuploid nuclei with a wide range of chromosome numbers, tetraploid and haploid nuclei. The frequency of aneuploid and polyploid cells was higher in callus grown in the presence of 2,4-D than in callus grown in NAA plus BAP. These nuclei seemed to increase with the duration of culture. The chromosome number distribution as determined by chromosome counts in calli at different culture times was confirmed by DNA cytophotometry. Chromosome number mosaicism (mixoploidy and aneusomaty) also occurred in all root apices of 9 out of 46 plantlets regenerated from callus via adventitious shoots. [ABSTRACT FROM AUTHOR]

Preimplantation genetic testing for aneuploidy (PGT-A) is widely used to identify aneuploidy embryos, thereby reducing miscarriage rate and improving the clinical outcome of in vitro fertilization (IVF). But there are many reasons for miscarriage. Not all miscarriages are caused by embryonic aneuploidy. Moreover, PGT-A has its inherent defects, the results of PGT-A may not fully represent the true karyotype of embryos. Many problems still exist in this technology: 1. Biases caused by whole genome amplification (WGA) or high-throughput detection techniques; 2.Embryo mosaicism. Therefore, it remains unclear what percentage of spontaneous abortion can be prevented by PGT-A. Since 2015, our center has adopted multiple displacement amplification (MDA) as the first step in all PGT cycles. So a complete library of MDA products has been well-established. We collected PGT cycles performed for monogenic diseases (PGT-M) at our center from January 2015 to December 2017. Cycles in which the blastocyst biopsy and single blastocyst transplantation were applied, and spontaneous miscarriage appeared during early pregnancy, and MDA products of the embryos were frozen were considered eligible. Exclusion criteria: cycles in which PGT-A had been conducted and the embryo was already selected according to the PGT-A results. All MDA products were performed PGT-A using next generation sequencing (NGS) by Illumina NextSeq ® 550 platform. The software determined the ploidy status with 0.01X read coverage. A total of 21 MDA products were detected, and 4 of them were unable to evaluate due to amplification failure or poor test data. The PGT-A results of the remaining 17 embryos showed that 47.1% (8/17) embryos were euploidy, 11.6% (2/17) embryos were segmental chromosomal aneuploidy (46,XN,-(1)(q23.3-q44)(85.03Mb) and 46,XN,+(13)(q11-q34)(95.75Mb)), 27.8% (5/18) of embryos were whole chromosomal aneuploidy mosaicism (the proportion of mosaicism range from 21 to 47%) and 2 cases were trisomy (trisomy 21 and trisomy 22). 6 patients performed karyotype analysis of abortion tissues, among which PGT-A results of 4 cases (3 cases were normal, one was trisomy 22) were consistent with the karyotype of abortion tissues. However, 2 cases showed aneuploidy mosaicism (46,XN,+(mosaic)(19)(30%) and 46,XN,-(mosaic)(6)(44%)) by PGT-A, while the karyotype of their abortion tissues were normal. Our study showed that PGT-A could prevent a proportion of spontaneous abortion. However, embryos with low ratio of mosaicism may not be the cause of miscarriage. In fact, spontaneous abortion of these cases was caused by other factors. How high the proportion of mosaicism may lead to miscarriage still requires further research to confirm. [ABSTRACT FROM AUTHOR]

Preimplantation genetic testing for aneuploidy(PGT-A) has been widely used, but its clinical application value is still inconclusive. The previous PGS 1.0 technology has been proven to have a negative impact on IVF outcomes. PGS 2.0, blastocyst biopsy combined with high-throughput detection technology, has gradually became the mainstream detection method of PGT-A.Many problems still exist in this technology: 1. Biases caused by whole genome amplification (WGA) or high-throughput detection techniques; 2.Embryo mosaicism.Mosaic embryos were used to be considered unsuitable for transfer. However recently healthy live births after transferring mosaic embryo have been widely reported. And many studies also found that some embryos diagnosed as abnormal by PGT-A were turned out to be normal after retested with their inner cell mass. It is therefore suggested that there may be false positive results in PGT-A technology, resulting in the waste of many valuable embryos with normal developmental potential. The interpretation of PGT-A results in clinical practice remains deficient.Since 2015, our center has adopted multiple displacement amplification (MDA) as the first step of all PGT cycles, so we have established a library of MDA products. We investigated PGT cycles conducted for monogenic diseases (PGT-M) between January 2015 and December 2017 in our center. Eligible cycles were in which the blastocyst biopsy and single blastocyst transfer were adopted and healthy live birth was obtained. Exclusion criteria: Cycles in which PGT-A had been performed and the embryo was selected based on PGT-A results. MDA used Repli-g MiDi kit(Qiagen, Germany) or Repli-g Single cell kit(Qiagen, Germany).All MDA products were conducted PGT-A using next generation sequencing (NGS) by Illumina NextSeq® 550 platform. We sequenced the amplified genome of each sample at approximately 0.01x genome depth and the resolution of chromosomal abnormality detection was 4Mb. A total of 103 MDA products were tested, of which 11 failed to amplify. Among the 92 successful amplified products, 47 used the Midi-MDA kit while 46 used the Single cell-MDA kit. The average standard deviation(SD) value of NGS data was 3.58 (2.09-9.25).The PGT-A results showed that: 35.9%(33/92) embryos were euploidy; one was trisomy 22; 30.4%(28/92) embryos were mosaic whole chromosomal aneuploidy (the proportion of mosaicism range from 20% to 41%);6.5% (6/92) embryos were segmental chromosomal aneuploidy(chromosomal fragment length of duplication or deletion range from 4.06 Mb to 191.01 Mb), and 8.7% (8/92) embryos were mosaic segmental aneuploidy; 17.4% (16/92) embryos had segmental aneuploidy combined with mosaic aneuploidy. Overall, mosaic chromosomal aneuploidy was detected in 56.5% (52/92) blastocysts which could produce healthy babies.Prenatal diagnosis or karyotype detection of the newborns were performed in 31 cases and all the results were euploidy. Our study demonstrated that PGT-A would lead to the waste of viable embryos, so it should be questioned whether all mosaic embryos and segmental aneuploidy embryos should be abandoned. How to correctly interpret the results of PGT-A is an urgent problem. [ABSTRACT FROM AUTHOR]