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

BACKGROUND

Turner syndrome (TS) is the most common sex chromosomal abnormality in females resulting from a missing X chromosomal material. This in turn results in a range of clinical manifestations. This study aimed to provide the data on the cases of TS confirmed via chromosomal analysis in a cytogenetics laboratory in the Philippines as well as the role of genetic counseling.

A review of the karyotyping results of the Cytogenetics Laboratory, Institute of Human Genetics, National Institutes of Health, University of the Philippine Manila from 1991 to 2020.

TS accounted for 2.64% of all the samples received from 1991 to 2020. For 30 years, the most common karyotype in TS was the classical TS or the standard monosomy 45, X noted in 195 patients or 37.69% of all patients diagnosed with TS. Mosaicism with a normal female karyotype was noted in 50 patients (9.62%). For the TS variants, the most common is isochromosome Xq seen in 125 patients (24.04%). This is followed by TS with marker chromosome in 55 patients (10.58%) and ring X chromosome in 23 patients (4.42%). Deletion Xp and deletion Xq were noted in 22 patients (4.23%) and 20 patients (3.85%), respectively.

From this study, it can be noted that chromosomal analysis or standard karyotyping is a vital and useful diagnostic tool in TS. The information obtained from it may be useful in clinical decision-making of families and healthcare providers. Its importance in providing adequate genetic counseling cannot be overemphasized.

Disorders of sex development (DSD) are characterized by atypical development of chromosomal, gonadal, or phenotypic sex. 45X,46XY mosaicism is a type of sex chromosome DSD which presents with a wide heterogeneity of manifestations. We report the case of a 13-year-old phenotypically female who presented with clitoromegaly at puberty. Testosterone level was elevated on serology. Out of the 50 cells examined, 43 cells had Monosomy X while 7 cells had a normal male karyotype. She was managed by a multidisciplinary team. Due to the presence of Y chromosome, the solid nodular structure seen on the right gonad in magnetic resonance imaging and the pain caused by the phallus, Laparoscopic bilateral gonadectomy, salpingectomy and clitoroplasty were done after a shared decision making. Histopathology revealed Gonadoblastoma and Germ cell neoplasia-in-situ of the right gonad justifying timely removal. She was then maintained on estrogen for induction of secondary sexual characteristics.

Humans ; Child ; Klinefelter Syndrome/complications* ; Lupus Erythematosus, Systemic/complications*

OBJECTIVE: To explore the prevalence and clinical manifestations of ring chromosomes among children featuring abnormal development. METHODS: From January 2015 to August 2021, 7574 children referred for abnormal development were selected, and their peripheral blood samples were subjected to G-banded chromosomal karyotyping analysis. RESULTS: Twelve cases of ring chromosomes were detected, which have yielded a prevalence of 0.16% and included 1 r(6), 2 r(9), 1 r(13), 1 r(14), 2 r(15), 1 r(21) and 3 r(X). The children had various clinical manifestations including growth and mental retardation, limb malformation, and congenital heart disease. For two children with r(9) and two with r(15) with similar breakpoints, one child with r(9) and one with r(15) only had growth retardation, whilst another with r(9) and another with r(15) also had peculiar facies and complex congenital heart disease. The r(X) has featured some manifestations of Turner syndrome. CONCLUSION Ring chromosomes are among the common causes for severe growth and mental retardation in children with diverse clinical phenotypes. Clinicians should pay attention to those with developmental anomalies and use chromosomal analysis to elucidate their genetic etiology.
Humans ; Ring Chromosomes ; Intellectual Disability/genetics* ; Turner Syndrome/genetics* ; Phenotype ; Heart Defects, Congenital/genetics*

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 explore the genetic characteristics of idic(X)(p11.22) in Turner syndrome (TS). METHODS: Two fetuses suspected for sex chromosome abnormalities or ultrasound abnormalities were selected from Chengdu Women's and Children's Central Hospital in October 2020 and June 2020, and amniotic fluid samples were collected for G-banded chromosomal karyotyping analysis, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH). RESULTS: The two fetuses were respectively found to have a karyotype of 45,X[47]/46,X,psu idic(X)(p11.2)[53] and 46,X,psu idic(X)(p11.2). CMA found that both had deletions in the Xp22.33p11.22 region and duplications in the p11.22q28 region. FISH showed that the centromeres in both fetuses had located on an isochromosome. CONCLUSION The combination of karyotyping analysis, FISH, and CMA is useful for the delineation of complex structural chromosomal aberrations. High-resolution CMA can accurately identify chromosomal breakpoints, which can provide a clue for elucidating the mechanism of chromosomal breakage and rearrangement.
Female ; Pregnancy ; Humans ; Turner Syndrome/genetics* ; In Situ Hybridization, Fluorescence ; Sex Chromosome Aberrations ; Centromere ; Prenatal Diagnosis

Objective: To investigate the clinicopathological characteristics of testicular biopsies from Klinefelter syndrome (KS) patients. Methods: The testicular biopsy specimens of 87 patients with KS (a total of 107 biopsy specimens) were collected from the Department of Pathology, Peking University Third Hospital, Beijing, China from January 2017 to July 2022. All patients were diagnosed as KS by peripheral blood karyotyping analysis. The testicular histopathologic features, testicular volume and hormone levels were evaluated retrospectively. The histopathologic analysis was used to assess the quantity and morphology of Leydig cells, the spermatogenic state of seminiferous tubules, the thickening of the basement membrane of seminiferous tubules and the changes of stroma. Results: Leydig cell proliferative nodules were seen in 95.3% (102/107) of KS testicular biopsy tissues. The eosinophilic inclusion bodies and lipofuscin in Leydig cells were found in 52.3% (56/107) and 57.9% (62/107) of specimens, respectively. The Sertoli cell only seminiferous tubules and the hyalinized tubules were found in 66.4% (71/107) and 76.6% (82/107) of the examined tissues, respectively. The tubules with complete spermatogenic arrest were found in 15.9% (17/107) of specimens, and 5.6% (6/107) of the specimens showed low spermatogenesis or incomplete spermatogenic arrest. In 85.0% (91/107) of the specimens, increased thick-walled small vessels with hyaline degeneration were identified. Conclusions: The most common features of KS testicular specimens are Leydig cell proliferative nodules, hyaline degeneration of seminiferous tubules and proliferation of thick-walled blood vessels. Testicular biopsy specimens of KS are rare. The pathologists can make a tentative diagnosis of KS based on the histological findings, combined with the ultrasound and laboratory results, which is helpful for further diagnosis and treatment of KS.
Male ; Humans ; Testis/pathology* ; Klinefelter Syndrome/pathology* ; Retrospective Studies ; Seminiferous Tubules/pathology* ; Biopsy

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*