Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.
Animals ; Humans ; Male ; Female ; Sertoli Cells/metabolism* ; Klinefelter Syndrome/genetics* ; Endothelial Cells ; Testis/metabolism* ; X Chromosome/metabolism* ; Mammals/genetics*

Long non-coding RNAs (lncRNAs) reportedly function as important modulators of gene regulation and malignant processes in the development of human cancers. The lncRNA JPX is a novel molecular switch for X chromosome inactivation and differentially expressed JPX has exhibited certain clinical correlations in several cancers. Notably, JPX participates in cancer growth, metastasis, and chemoresistance, by acting as a competing endogenous RNA for microRNA, interacting with proteins, and regulating some specific signaling pathways. Moreover, JPX may serve as a potential biomarker and therapeutic target for the diagnosis, prognosis, and treatment of cancer. The present article summarizes our current understanding of the structure, expression, and function of JPX in malignant cancer processes and discusses its molecular mechanisms and potential applications in cancer biology and medicine.
Humans ; RNA, Long Noncoding/genetics* ; Neoplasms/genetics* ; MicroRNAs/genetics* ; Gene Expression Regulation ; X Chromosome Inactivation

OBJECTIVE: To explore the genetic basis for a child with febrile seizures. METHODS: Peripheral venous blood samples were taken from the child and his parents for the analysis of chromosomal karyotype and dynamic variant of the FMR1 gene. The family trio was also subjected to target capture and next generation sequencing (NGS) with a gene panel related to developmental retardation, mental retardation, language retardation, epilepsy and special facial features. RESULTS: The child was found to have a normal karyotype by conventional cytogenetic analysis (400 bands). No abnormal expansion was found with the CGG repeats of the FMR1 gene. NGS revealed that the child has carried a heterozygous c.864+1 delG variant of the MEF2C gene, which may lead to abnormal splicing and affect its protein function. The same variant was found in neither parent, suggesting that it has a de novo origin. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.864+1delG variant of MEF2C gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION MEF2C, as the key gene for chromosome 5q14.3 deletion syndrome which was speculated as a cause for febrile seizures, has an autosomal dominant effect. The c.864+1delG variant of the MEF2C gene may account for the febrile seizures in this patient.
Child ; Chromosome Deletion ; Chromosome Disorders ; Epilepsy ; Fragile X Mental Retardation Protein ; Humans ; Intellectual Disability/genetics* ; Karyotyping ; MEF2 Transcription Factors/genetics*

OBJECTIVE: To explore the genetic basis for a child featuring short stature, saddle nose, cryptorchidism and mental retardation. METHODS: The child and his parents were subjected to G-banded karyotyping and chromosomal microarray analysis (CMA). RESULTS: The child was found to have a 46,Y,der(X)t(X;Y)(p22;q11)mat karyotype. CMA has revealed a 8.3 Mb deletion at Xp22.33p22.31 and a 43.3 Mb duplication at Yq11.221qter. His mother had a karyotype of 46,X,der(X)t(X;Y)(p22;q11). His father had a normal karyotype. CONCLUSION The child has carried an unbalanced translocation der(X)t(X;Y) (p22;q11) derived from his mother. His clinical phenotype has correlated with the size and position of X chromosome deletion. Compared with the females, abnormal phenotypes such as mental retardation and growth retardation of male carriers are more severe.
Child ; Chromosome Banding ; Chromosomes, Human, X/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Translocation, Genetic

OBJECTIVE: To explore the pathogenesis and genetic characteristics of a fetus with a der(X)t(X;Y)(p22.3;q11.2) karyotype. METHODS: G-banding karyotyping analysis, BoBs (BACs-on-Beads) assay, and single nucleotide polymorphism array (SNP-array) were used to delineate the structural chromosomal aberration of the fetus. The parents of the fetus were also subjected to karyotyping analysis. RESULTS: The fetus and its mother were both found to have a karyotype of 46,X,add(X)(p22), while the father was normal. BoBs assay indicated that there was a lack of Xp22 but a gain of Yq11 signal. SNP-array confirmed that the fetus and its mother both had a 7.13 Mb deletion at Xp22.33p22.31 (608 021-7 736 547) and gain of a 12.52 Mb fragment at Yq11.221q11.23 (16 271 151-28 788 643). CONCLUSION The fetus was determined to have a karyotype of 46,X,der(X)t(X;Y)(p22.3;q11.2)mat. The combined use of various methods has facilitated delineation of the fetal chromosomal aberration and prediction of the risk prediction for subsequent pregnancy.
Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, X/genetics* ; Chromosomes, Human, Y/genetics* ; Female ; Fetus ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic

OBJECTIVE: To explore the genetic basis for a fetus with cleft lip and palate. METHODS: Copy number variations (CNVs) in the fetus and his parents were detected with chromosomal microarray analysis (CMA). RESULTS: As revealed by the CMA assay, the fetus has carried a 228 kb deletion in Xp11.22 region and a 721 kb duplication in 9p21.1. Both CNVs were inherited from the parents. The CNV in Xp11.22 was predicted to be pathogenic by involving the PHF8 gene, whilst the CNV in 9p21.1 was predicted to be benign. CONCLUSION Deletion of the Xp11.22 region probably underlies the cleft lip and palate in this fetus.
Chromosome Deletion ; Chromosomes, Human, X ; genetics ; Cleft Lip ; diagnosis ; genetics ; Cleft Palate ; diagnosis ; genetics ; DNA Copy Number Variations ; Female ; Fetus ; Histone Demethylases ; Humans ; Microarray Analysis ; methods ; Pregnancy ; Prenatal Diagnosis ; Transcription Factors

OBJECTIVETo report on a sporadic case of Lowe syndrome diagnosed prenatally with ultrasound examination and genetic testing.

METHODSDetailed sonographic fetal screening was performed by an experienced sonographer at 32 weeks of gestation. Fetal cranial magnetic resonance imaging (MRI) was applied to detect potential brain abnormality. Chromosomal microarray analysis (CMA) was conducted on amniotic fluid sample from the fetus and peripheral blood sample from the mother.

RESULTSCongenital cataract and enlarged posterior fossa were detected by fetal ultrasound screening. Fetal cranial MRI found hypoplasia of the gyrus. CMA revealed that the fetus has carried a 633 kb deletion at Xq25-26.1 which encompassed the OCRL gene. The mother was a carrier of the same deletion. Clinical examination after birth confirmed that the neonate was affected with Lowe syndrome in addition with an atrial septal defect.

CONCLUSIONPrenatal diagnosis of Lowe syndrome without a family history largely depends on fetal imaging. Should cataract be found by ultrasound screening, fetal MRI may be considered to rule out central nervous system anomalies. CMA assay should also be considered to facilitate the diagnosis.

Adult ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, X ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Infant ; Male ; Microarray Analysis ; Oculocerebrorenal Syndrome ; diagnosis ; embryology ; genetics ; Phosphoric Monoester Hydrolases ; genetics ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal

OBJECTIVETo analyze partial deletion of the long arm of X chromosome in a family and explore the mechanism underlying its phenotypes.

METHODSG-banding technique was employed to analyze the karyotypes of the subjects, and fluorescence in situ hybridization (FISH) was used to analyze their X chromosomes with Xpter, Xqter and WCPX probes.

RESULTSThe karyotypes of the proband, her mother and her fetus were all 46,X,del(X)(q24). Combined FISH and karyotyping analysis suggested that the proband and her fetus both carried a Xq24q27.3 deletion.

CONCLUSIONThe Xq24q27.3 deletion carried by the family is closely related with premature ovarian failure but not with short stature, gonadal dysgenesis and primary amenorrhea.

Adult ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, X ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Primary Ovarian Insufficiency ; genetics

OBJECTIVETo explore the correlation between cytogenetic findings and clinical manifestations of Turner syndrome.

METHODS607 cases of cytogenetically diagnosed Turner syndrome, including those with a major manifestation of Turner syndrome, were analyzed with conventional G-banding. Correlation between the karyotypes and clinical features were analyzed.

RESULTSAmong the 607 cases, there were 154 cases with monosomy X (25.37%). Mosaicism monosomy X was found in 240 patients (39.54%), which included 194 (80.83%) with a low proportion of 45,X (3 ≤ the number of 45, X ≤5, while the normal cells ≥ 30). Structural X chromosome abnormalities were found in 173 patients (28.50%). A supernumerary marker chromosome was found in 40 cases (6.59%). Most patients with typical manifestations of Turner syndrome were under 11 years of age and whose karyotypes were mainly 45,X. The karyotype of patients between 11 and 18 years old was mainly 45,X, 46,X,i(X)(q10) and mos45,X/46,X,i(X)(q10), which all had primary amenorrhea in addition to the typical clinical manifestations. The karyotype of patients over 18 years of age were mainly mosaicism with a low proportion of 45,X, whom all had primary infertility. 53 patients had a history of pregnancy, which included 48 with non-structural abnormalities of X chromosome and 5 with abnormal structure of X chromosome.

CONCLUSIONGenerally, the higher proportion of cells with an abnormal karyotype, the more severe were the clinical symptoms and the earlier clinical recognition. Karyotyping analysis can provide guidance for the early diagnosis of Turner syndrome, especially those with a low proportion of 45,X.

Abortion, Spontaneous ; genetics ; Adolescent ; Adult ; Amenorrhea ; genetics ; Child ; Child, Preschool ; Chromosomes, Human, X ; genetics ; Cytogenetic Analysis ; methods ; Female ; Humans ; Infant ; Infant, Newborn ; Karyotyping ; Middle Aged ; Mosaicism ; Pregnancy ; Sex Chromosome Aberrations ; Turner Syndrome ; genetics ; pathology ; Young Adult

OBJECTIVETo analyze a fetus with increased nuchal translucency and nuchal fold, and to assess the recurrence risk for her family and provide a basis for prenatal diagnosis.

METHODSG-banded karyotyping and single nucleotide polymorphism-based array (SNP-Array) analysis were used to analyze the fetus and her parents.

RESULTSSNP-Array analysis has detected a 41.04 Mb duplication at Xp22.33p11.4 and a 30.51 Mb duplication at 13q31.3q34 in the fetus. G-banding karyotyping indicated that the fetus had a karyotype of 46,X,der(X)(13qter-13q31::Xp11.4-Xp22.3::Xp22.3-Xqter). Her parents had normal results for both G-banding karyotyping and SNP-Array analysis, suggesting that the fetus has carried a de novo derivative chromosome X.

CONCLUSIONSNP-Array combined with G-banding karyotyping is helpful to confirm the composition and connection type of de novo derivative chromosome, which can improve the accuracy of diagnosis and is valuable for the evaluation of recurrence risk.

Adult ; Chromosome Banding ; Chromosome Duplication ; Chromosomes, Human, X ; genetics ; Female ; Fetus ; abnormalities ; metabolism ; Humans ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; methods ; Sex Chromosome Aberrations