Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations

OBJECTIVE: To analyze the effect of Y chromosome AZFc microdeletion on pregnancy outcome of intracytoplasmic sperm injection (ICSI). METHODS: From 2016 to 2023, 6 765 cases of oligozoospermia in our hospital were selected as the research objects. The results of Y chromosome microdeletion test were retrospectively analyzed. According to the inclusion exclusion criteria and the principle of propensity distribution 1∶2, 180 patients were included in the study. Sixty patients with Y chromosome AZFc microdeletion and ICSI assisted pregnancy were enrolled into the experimental group. The other 120 patients without Y chromosome microdeletion and ICSI assisted pregnancy were included in the control group. Baseline characteristics, five male sex hormones, laboratory embryo culture and pregnancy outcomes were compared between the two groups. RESULTS: There was no significant difference in male age, female age, infertility years, gravidity and parity between the two groups (P>0.05). There was no significant difference in the five sex hormones of men (P>0.05). Except for transplantable embryos (P<0.05), there was no significant difference in other indicators in the process of embryo culture. There was no difference in pregnancy outcome indicators between the two groups except for the preterm birth rate (P<0.05). CONCLUSION ICSI assisted pregnancy with Y chromosome AZFc microdeletion has no significant effect on pregnancy outcome. And close follow-up of offspring is required.
Humans ; Sperm Injections, Intracytoplasmic ; Pregnancy ; Female ; Chromosomes, Human, Y ; Male ; Chromosome Deletion ; Pregnancy Outcome ; Retrospective Studies ; Sex Chromosome Disorders of Sex Development ; Sex Chromosome Aberrations ; Adult ; Infertility, Male/genetics* ; Oligospermia/genetics* ; Pregnancy Rate

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD). METHODS: Five children with DSD who presented at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled. In addition to chromosomal karyotyping, whole exome sequencing (WES), SRY gene testing, and CNV-seq were also carried out. RESULTS: Child 1 and 2 had a social gender of female, whilst their karyotypes were both 46,XY. No pathogenic variant was identified by WES. The results of CNV-seq were 46,XY,+Y (1.4) and 46,XY,-Y (0.75), respectively. The remaining three children have all carried an abnormal chromosome Y. Based on the results of CNV-seq, their karyotypes were respectively verified as 45,X[60]/46,X,del(Y)(q11.221)[40], 45,X,16qh+[76]/46,X,del(Y)(q11.222),16qh+[24], and 45,X[75]/46,XY[25]. CONCLUSION CNV-seq may be used to verify the CNVs on the Y chromosome among children with DSD and identify the abnormal chromosome in those with 45,X/46,XY. Above results have provided a basis for the clinical diagnosis and treatment of such children.
Humans ; Child ; Female ; DNA Copy Number Variations ; Chromosome Aberrations ; Karyotyping ; Exome Sequencing ; Disorders of Sex Development/genetics*

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the prenatal diagnosis of chromosomal mosaicisms. METHODS: A total of 775 pregnant women who had visited the Prenatal Diagnosis Center of Yancheng Maternal and Child Health Care Hospital from January 2018 to December 2020 were selected as study subjects. Chromosome karyotyping analysis and CMA were carried out for all women, and FISH was used to validate the suspected mosaicism cases. RESULTS: Among the 775 amniotic fluid samples, karyotyping has identified 13 mosaicism cases, which yielded a detection rate of 1.55%. Respectively, there were 4, 3, 4 and 2 cases for sex chromosome number mosaicisms, abnormal sex chromosome structure mosaicisms, abnormal autosomal number mosaicisms and abnormal autosomal structure mosaicisms. CMA has only detected only 6 of the 13 cases. Among 3 cases verified by FISH, 2 cases were consistent with the karyotyping and CMA results, and clearly showed low proportion mosaicism, and 1 case was consistent with the result of karyotyping but with a normal result by CMA. Eight pregnant women had chosen to terminate the pregnancy (5 with sex chromosome mosaicisms and 3 with autosomal mosaicisms). CONCLUSION For fetuses suspected for chromosomal mosaicisms, CMA, FISH and G-banding karyotyping should be combined to determine the type and proportion of mosaicisms more precisely in order to provide more information for genetic counseling.
Female ; Pregnancy ; Humans ; Mosaicism ; In Situ Hybridization, Fluorescence ; Chromosome Disorders/genetics* ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Sex Chromosome Aberrations ; Microarray Analysis/methods* ; Chromosomes

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women. METHODS: A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes. RESULTS: Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found. CONCLUSION NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.
Child ; Female ; Pregnancy ; Humans ; Retrospective Studies ; Cell-Free Nucleic Acids ; Chromosome Disorders/genetics* ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Sex Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Trisomy 13 Syndrome/diagnosis* ; Aneuploidy ; DNA/genetics* ; Trisomy/genetics*

OBJECTIVE: To retrospectively analyze sex chromosomal abnormalities and clinical manifestations of children with disorders of sex development (DSD). METHODS: A total of 14 857 children with clinical features of DSD including short stature, cryptorchidism, hypospadia, buried penis and developmental delay were recruited from Zhengzhou Children's Hospital from January 2013 to March 2022. Fluorescence in situ hybridization (FISH) and chromosomal karyotyping were carried out for such children. RESULTS: In total 423 children were found to harbor sex chromosome abnormalities, which has yielded a detection rate of 2.85%. There were 327 cases (77.30%) with Turner syndrome and a 45,X karyotype or its mosaicism. Among these, 325 were females with short stature as the main clinical manifestation, 2 were males with short stature, cryptorchidism and hypospadia as the main manifestations. Sixty-two children (14.66%) had a 47,XXY karyotype or its mosaicism, and showed characteristics of Klinefelter syndrome (KS) including cryptorchidism, buried penis and hypospadia. Nineteen cases (4.49%) had sex chromosome mosaicisms (XO/XY), which included 11 females with short stature, 8 males with hypospadia, and 6 cases with cryptorchidism, buried penis, testicular torsion and hypospadia. The remainder 15 cases (3.55%) included 9 children with a XYY karyotype or mosaicisms, with main clinical manifestations including cryptorchidisms and hypospadia, 4 children with a 47,XXX karyotype and clinical manifestations including short stature and labial adhesion, 1 child with a 46,XX/46,XY karyotype and clinical manifestations including micropenis, hypospadia, syndactyly and polydactyly, and 1 case with XXXX syndrome and clinical manifestations including growth retardation. CONCLUSION Among children with DSD due to sex chromosomal abnormalities, sex chromosome characteristics consistent with Turner syndrome was most common, among which mosaicism (XO/XX) was the commonest. In terms of clinical manifestations, the females mainly featured short stature, while males mainly featured external genital abnormalities. Early diagnosis and treatment are particularly important for improving the quality of life in such children.
Humans ; Male ; Female ; Turner Syndrome/genetics* ; In Situ Hybridization, Fluorescence ; Cryptorchidism ; Hypospadias ; Retrospective Studies ; Quality of Life ; Sex Chromosome Aberrations ; Karyotyping ; Mosaicism ; Disorders of Sex Development/genetics*

OBJECTIVE: To explore the genetic basis of three children with disorders of sex development (DSD) in association with rare Y chromosome rearrangements. METHODS: The three children, who all featured short stature and DSD, were subjected to G banding chromosomal karyotyping, multiplex PCR for Y chromosomal microdeletion, sequencing of the whole SRY gene, SNP-array analysis for genomic copy number variations, and fluorescence in situ hybridization (FISH). RESULTS: The combined analysis revealed chromosomal abnormalities in all of the three children, including 46,X,t(X;Y)(p22.3;q11.2) in case 1, mos 45,X,der(7)pus dic(Y:7)(p11.3p22)del(7)(p21.2p21.3) del(7)(p12.3p14.3) [56]/45,X [44] in case 2, and mos 45,X [50]/46,X,idic(Y)(q11.22) [42]/47,X,idem×2 [4]/47,XYY [2] in case 3. CONCLUSION Combined use of genetic techniques can delineate complex rearrangements involving Y chromosome in patients featuring short stature and DSD. Above findings have enabled molecular diagnosis and genetic counseling for the patients.
Child ; Chromosome Banding ; Chromosomes, Human, Y/genetics* ; DNA Copy Number Variations ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Polymorphism, Single Nucleotide ; Sex Chromosome Aberrations ; Sex Chromosome Disorders of Sex Development/genetics*

ObjectiveTo identify the etiology of chromosome abnormality in an infertile man and analyze the correlation between the genotype and phenotype.

METHODSWe analyzed the karyotype of an infertile male using the routine G-banding technique and then the chromosome abnormality of the patient by Illumina Human CytoSNP-12 Beadchip array.

RESULTSNegative results were found in the examination of the sex-determining region Y (SRY) gene and the STR locus in the AZF zone of the patient. The karyotype of the patient was 46, XX. SNP array showed a 1.05 Mb 19p12 duplication and a 0.93 Mb Xq27.1 duplication.

CONCLUSIONSThe patient was confirmed as a case of 46,XX male syndrome. The increased copies of the FGF13 gene may be the major causes of abnormal sex determination and testis development.

46, XX Testicular Disorders of Sex Development ; diagnosis ; genetics ; Chromosome Aberrations ; Chromosome Banding ; Genetic Testing ; Humans ; Infertility, Male ; genetics ; Karyotype ; Karyotyping ; Male ; Phenotype ; Sex-Determining Region Y Protein ; genetics

Background: The 47,XYY syndrome could result in fertility problems. However, seldom studies reported comprehensive researches on the embryonic development and pregnancy outcomes of these patients. This study aimed to evaluate the clinical outcomes of nonmosaic 47,XYY patients performed with fluorescent in situ hybridization (FISH) and preimplantation genetic diagnosis (PGD) treatment. Methods: This was a retrospective study. Between January 2012 and May 2017, 51 infertile males with nonmosaic 47,XYY syndrome underwent FISH-PGD were included in the study. According to sex chromosomal FISH results, embryos were classified as normal signal, no nuclei fixed, no signal in fixed nuclei, suspensive signal, and abnormal signal groups, respectively. The incidence of each group, the fixation rate, and hybridization rate were calculated. Embryonic development and pregnancy outcomes were also analyzed. The measurement data were analyzed with Student's t-test. The comparison of categorical data was analyzed with the Chi-square test and Fisher's exact test when expected cell count was <5. Results: The 53 PGD cycles with 433 embryos were analyzed. The fixation rate was 89.6%, while the hybridization rate was 96.4%. There were 283 embryos with two sex chromosomal signals with clear diagnosis (65.4%). The numbers of no nuclei fixed, no signal in fixed nuclei, suspensive signal, and abnormal signal groups were 45 (10.4%), 14 (3.2%), 24 (5.5%), and 67 (15.5%), respectively. Embryos with abnormal signals were abandoned. The number of good-quality embryos was 210 (57.4%), including implanted embryos on day 4/day 5 and cryopreserved. The rates of good-quality embryos in the no nuclei fixed (22.2%), no signal in fixed nuclei (28.6%), and suspensive signal groups (33.3%) were comparable (P > 0.05), and were significantly lower than the normal signal group (66.4%, P < 0.001). The clinical pregnancy rates of fresh and frozen embryos transferred cycles were 70.6% and 85.7%, respectively. Conclusions Among embryos with a clear diagnosis of sex chromosome, about one-fifth showed abnormal signals. Embryos with two sex chromosomal signals are more likely to develop into good-quality ones. The application of the PGD by FISH may help to improve the clinical outcome s.
Female ; Humans ; In Situ Hybridization, Fluorescence ; Infertility, Male ; genetics ; Male ; Pregnancy ; Preimplantation Diagnosis ; Retrospective Studies ; Sex Chromosome Disorders ; diagnosis ; genetics ; XYY Karyotype ; diagnosis ; genetics

ObjectiveTo investigate the clinical (including reproductive) manifestations and genetic characteristics of familial fragile X syndrome (FXS).

METHODSWe collected the clinical data about a case of familial FXS by inquiry, testicular ultrasonography, semen analysis, determination of sex hormone levels, and examinations of the peripheral blood karyotype and Y chromosome microdeletions. Using Southern blot hybridization, we measured the size of the CGG triple repeat sequence of the fragile X mental retardation-1 (FMR1) gene and determined its mutation type of the pedigree members with a genetic map of the FXS pedigree.

RESULTSAmong the 34 members of 4 generations in the pedigree, 3 males and 1 female (11.76%) carried full mutation and 9 females (26.47%) premutation of the FMR1 gene. Two of the males with full FMR1 mutation, including the proband showed a larger testis volume (>30 ml) and a higher sperm concentration (>250 ×10⁶/ml), with a mean sperm motility of 50.5%, a mean morphologically normal sperm rate of 17.5%, an average sperm nuclear DNA fragmentation index (DFI) of 18.5%, a low level of testosterone, normal karyotype in the peripheral blood, and integrity of the azoospermia factor (AZF) region in the Y chromosome. One of the second-generation females carrying FMR1 premutation was diagnosed with premature ovarian failure and another 3 with uterine myoma.

CONCLUSIONSSome of the FXS males in the pedigree may present macroorchidism and polyzoospermia but with normal semen parameters. In the intergenerational transmission, premutation might extend to full mutation, with even higher risks of transmission and extension of mutation in males, especially in those with >80 CGG triple repeat sequences. Therefore, it is recommended that the couples wishing for childbearing receive genetic testing, clinical guidance, and genetic counseling before pregnancy and, if necessary, prenatal diagnosis and preimplantation genetic diagnosis.

Chromosome Deletion ; Chromosomes, Human, Y ; genetics ; DNA Fragmentation ; Female ; Fragile X Mental Retardation Protein ; genetics ; Fragile X Syndrome ; genetics ; Genetic Testing ; Humans ; Infertility, Male ; genetics ; Karyotyping ; Male ; Mutation ; Organ Size ; Pedigree ; Pregnancy ; Preimplantation Diagnosis ; Risk ; Sex Chromosome Aberrations ; Sex Chromosome Disorders of Sex Development ; genetics ; Sperm Count ; Testis ; diagnostic imaging ; pathology