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

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*

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 determine the chromosomal karyotype of a fetus with copy number variation (CNV) of the X chromosome signaled by non-invasive prenatal testing (NIPT). METHODS: NIPT was performed on the peripheral blood sample taken from the pregnant women. Amniotic fluid and cord blood samples were subjected to conventional G banded karyotyping, and were further analyzed by high-throughput sequencing for chromosome microdeletion/microduplication. The results were then verified by fluorescence in situ hybridization (FISH) on metaphase cells. RESULTS: The NIPT test of pregnant women suggested low risk for 21-trisomy, 18-trisomy, and 13-trisomy, whilst indicated the number of chromosome X to be low. The G banded karyotype of the amniotic fluid and cord blood cells was 46,XX. The result of high-throughput sequencing chromosome microdeletion/microduplication detection was seq[hg19](X)× 1, (Y)× 2. FISH showed a clear red signal at each end of a whole chromosome, and a green signal on the other chromosome, with a karyotype of 46,X,ish idic(Y) (q11.23) (SRY++, DXZ1+). C banding showed that there is a dense and a slightly loose centromere at both ends of the Y chromosome, and the parachromatin region was missing. The karyotype of amniotic fluid and cord blood cells was finally determined to be 46,X, pus idic(Y) (q11.23). CONCLUSION For chromosome anomalies suggested by auxiliary report of NIPT, conventional karyotyping combined with high-throughput sequencing for chromosome microdeletion/microduplication should be adopted for the prevention and reduction of the rate of chromosome microdeletion/microduplication syndromes.
Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Pregnancy ; Prenatal Diagnosis ; X Chromosome

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

Filamin A is an actin-binding protein and, in humans, is encoded by FLNA gene in the long arm of X chromosome. Filamin A plays a role in the formation of cytoskeleton by crosslinking actin filaments in cytoplasm. FLNA mutations affect cytoskeletal regulatory processes and cellular migrating abnormalities that result in periventricular heterotopia. A 5-month-old girl was hospitalized because of breathing difficulty and was diagnosed as having periventricular heterotopia with laryngomalacia, cricopharyngeal incoordination, pulmonary hypertension, and chronic lung disease. A genetic test was performed to find the cause of periventricular heterotopia, and FLNA gene mutation (c.5998+1G>A) was confirmed for the first time in Korea. After discharge, she developed respiratory failure due to a viral infection at 8 months of her age. In spite of management with mechanical ventilation, she died of pneumothorax and pulmonary hemorrhage. Herein, we report a case of FLNA gene mutation who presented with periventricular nodular heterotopia with respiratory insufficiency.
Actin Cytoskeleton ; Arm ; Ataxia ; Cytoplasm ; Cytoskeleton ; Female ; Filamins ; Hemorrhage ; Humans ; Hypertension, Pulmonary ; Infant ; Korea ; Laryngomalacia ; Lung Diseases ; Periventricular Nodular Heterotopia ; Pneumothorax ; Respiration ; Respiration, Artificial ; Respiratory Insufficiency ; X Chromosome

Klinefelter syndrome (KS) is characterized by small testes, gynecomastia, tall stature, and hypergonadotropic hypogonadism. This condition is associated with extra X chromosomes. It is well known that these aneuploidies predispose individuals to the development of several cancers. Moreover, there are many case reports that show KS patients to have a higher relative risk for the development of malignancy. However, incracranial germ cell tumor (ICGCT) associated with KS is very uncommon. Herein, we report delayed diagnosis of KS in a 15-year-old boy with ICGCT, embryonal carcinoma of the pineal gland, after multimodality treatment in Korea.
Adolescent ; Aneuploidy ; Carcinoma, Embryonal ; Delayed Diagnosis ; Gynecomastia ; Humans ; Hypogonadism ; Klinefelter Syndrome ; Korea ; Male ; Neoplasms, Germ Cell and Embryonal ; Pineal Gland ; Testis ; X Chromosome

Biological sex (being female or male) significantly influences the course of disease. This simple fact must be considered in all cardiovascular diagnosis and therapy. However, major gaps in knowledge about and awareness of cardiovascular disease in women still impede the implementation of sex-specific strategies. Among the gaps are a lack of understanding of the pathophysiology of women-biased coronary artery disease syndromes (spasms, dissections, Takotsubo syndrome), sex differences in cardiomyopathies and heart failure, a higher prevalence of cardiomyopathies with sarcomeric mutations in men, a higher prevalence of heart failure with preserved ejection fraction in women, and sex-specific disease mechanisms, as well as sex differences in sudden cardiac arrest and long QT syndrome. Basic research strategies must do more to include female-specific aspects of disease such as the genetic imbalance of 2 versus one X chromosome and the effects of sex hormones. Drug therapy in women also needs more attention. Furthermore, pregnancy-associated cardiovascular disease must be considered a potential risk factor in women, including pregnancy-related coronary artery dissection, preeclampsia, and peripartum cardiomyopathy. Finally, the sociocultural dimension of gender should be included in research efforts. The organization of gender medicine must be established as a cross-sectional discipline but also as a centered structure with its own research resources, methods, and questions.
Cardiomyopathies ; Cardiovascular Diseases ; Coronary Artery Disease ; Coronary Vessels ; Death, Sudden, Cardiac ; Diagnosis ; Drug Therapy ; Female ; Gonadal Steroid Hormones ; Heart Failure ; Humans ; Long QT Syndrome ; Male ; Peripartum Period ; Pre-Eclampsia ; Prevalence ; Risk Factors ; Sex Characteristics ; X Chromosome