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*

OBJECTIVETo analyze intron 1 and 22 inversions in factor VIII (FVIII) gene in hemophilia A (HA) patients and and their families and to investigate the correlation between intron inversion and FVIII antibody.

METHODSAll patients were detected FVIII: C and FVIII antibody. In addition, 81 unrelated HA patients were directly detected by multiplex PCR and long-distance PCR for intron 1 and 22 inversions in FVIII gene. Pedigree investigation for some patients were conducted.

RESULTSIn 81 unrelated HA patients, 3 severe cases were found intron 1 inversion which accounted for 4.6% of total 65 severe cases. Of the 3 cases, one was FVIII antibody positive. Two female family members of a intron 1 inversion patient were identified as one carrier and one non-carrier. Twenty five of 65 (38.5%) severe cases were found intron 22 inversion. Of the 25 cases 1 was FVIII antibody positive. Nine female members in 5 HA families which had patients with intron 22 inversion were identified as 7 carries and 2 non-carriers.

CONCLUSIONBesides intron 22 inversion, intron 1 inversion was another important molecular defect in resulting in severe HA. Intron inversion analysis can also be used for deviation rectification of experiment grouping in HA patients. Intron 1 and 22 inversions may be one of the higher risk factors for resulting in FVIII antibodies.

Chromosome Inversion ; Chromosomes, Human, X ; Factor VIII ; genetics ; Female ; Hemophilia A ; genetics ; Humans ; Introns ; Male

OBJECTIVERett syndrome (RTT) is a neurodevelopmental disorder occurring almost exclusively in females as sporadic cases due to de novo mutations in the methyl-CpG-binding protein 2 gene (MECP2). Familial cases of RTT are rare and are due to X-chromosomal inheritance from a carrier mother. Recently, DNA mutations in the MECP2 have been detected in approximately 84.7% of patients with RTT in China. To explain the sex-limited expression of RTT, it has been suggested that de novo X-linked mutations occur exclusively in male germ cells resulting therefore only in affected daughters. To test this hypothesis, we have analyzed the parental origin of mutations and the XCI status in 15 sporadic cases with RTT due to MECP2 molecular defects.

METHODSAllele-specific PCR was performed to amplify a fragment including the position of the mutation. The allele-specific PCR products were sequenced to determine which haplotype contained the mutation. It was then possible to determine the parent of origin by genotyping the single nucleotide polymorphism (SNP) in the parents. The degree of XCI and its direction relative to the X chromosome parent of origin were measured in DNA prepared from peripheral blood leucocytes by analyzing CAG repeat polymorphism in the androgen receptor gene (AR).

RESULTSExcept for 2 cases who had a frameshift mutation; all the remaining 13 cases had a C-->T transition mutation. Paternal origin has been determined in all cases with the C-->T transition mutation. For the two frameshift mutations, paternal origin has been determined in one case and maternal origin in the other. The frequency of male germ-line transmission in mutations is 93.3%. Except for 2 cases who were homozygotic at the AR locus, of the remaining 13 cases, 8 cases had a random XCI pattern; the other five cases had a skewed XCI pattern and they favor expression of the maternal origin allele.

CONCLUSIONDe novo mutations in sporadic RTT occur almost exclusively on the paternally derived X chromosome and that this is most probably the cause for the high female: male ratio observed in sporadic cases with RTT. Random XCI was the main XCI pattern in sporadic RTT patients. The priority inactive X chromosome was mainly of paternal origin.

Chromosome Aberrations ; Chromosomes, Human, X ; Female ; Humans ; Male ; Methyl-CpG-Binding Protein 2 ; genetics ; Mutation ; Polymorphism, Single Nucleotide ; Rett Syndrome ; genetics ; X Chromosome Inactivation

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

Adrenal Insufficiency ; genetics ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, X ; genetics ; Gene Deletion ; Glycerol Kinase ; deficiency ; genetics ; Humans ; Male ; Muscular Dystrophy, Duchenne ; genetics ; Sex Chromosome Aberrations

The objective of this study was to elucidate the cause of the spermatogenic defect in idiopathic azoospermia and non-mosaic type of Klinefelter syndrome. Genomic DNAs from 9 cases of Korean idiopathic azoospermia and 6 of Korean non-mosaic type of Klinefelter syndrome were used for the detection of Y chromosome microdeletions by polymerase chain reaction using 60 primers. Microdeletions of the Y chromosome were found in 1 of 9 (11.1%) patients with idiopathic azoospermia, whereas none was deleted in non-mosaic type of Klinefelter syndrome. This result suggests that Y chromosome microdeletions could be one of the etiologic factors in idiopathic azoospermia.
Gene Dosage ; Human ; Klinefelter Syndrome/classification/*genetics ; Male ; Oligospermia/classification/*genetics ; Polymerase Chain Reaction ; *Sequence Deletion ; Sequence Tagged Sites ; Spermatogenesis ; X Chromosome/genetics ; Y Chromosome/*genetics

OBJECTIVETo explore the pathogenetic mechanism for a female patient affected with hemophilia A (HA).

METHODSPotential genetic defect was detected with inverse shifting-polymerase chain reaction (IS-PCR). The pattern of X chromosome inactivation was determined with a human androgen receptor assay (HUMARA assay). G-banded karyotyping was carried out to exclude potential chromosome aberrations.

RESULTSIS-PCR showed that the defect of FVIII gene was the distal type of intron 22 inversion. The HUMARA assay showed that the X chromosome inactivation was non-random, and that the mother's X chromosome activity was lower than that of the father's X chromosome which has carried the inverted FVIII gene. No abnormalities were found with G-banded chromosomes.

CONCLUSIONThe prevalence of female HA patient may be caused by non-random inactivation of X chromosomes.

Adolescent ; Female ; Hemophilia A ; etiology ; genetics ; Humans ; Karyotyping ; Polymerase Chain Reaction ; Receptors, Androgen ; analysis ; X Chromosome Inactivation

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

Major aneuploidies diagnosed prenatally involve the autosomes 13, 18, and 21, and sex chromosomes. Fluorescence in situ hybridization (FISH) allows rapid analysis of chromosome copy number in interphase cells. The purpose of this study was to evaluate the role of multicolor fluorescence in situ hybridization in simultaneous detection of probe sets for chromosome 18, X, and Y in uncultured amniotic fluid cells as a safer alternative method for aneuploidy detection prenatally. Fifty amniotic fluid samples were analyzed by FISH and standard cytogenetics. Mean time to obtain results was three days for fluorescence in situ hybridization and 20 days for karyotype. Fluorescence in situ hybridization was informative in 43 samples (86%), and within this group, two aneuploidies were correctly identified. This evaluation demonstrates that FISH with X, Y, and 18 alpha satellite DNA probes could accurately and rapidly detect aneuploidies involving these chromosomes and could be used in any prenatal clinical laboratory.
Amniocentesis/methods* ; Amniotic Fluid/cytology ; Aneuploidy ; Centromere/genetics ; Chromosomes, Human, Pair 18* ; Color ; DNA Probes ; DNA, Satellite/analysis ; Female ; Human ; In Situ Hybridization, Fluorescence/methods* ; Karyotyping ; Pregnancy ; Sex Chromosome Abnormalities/genetics ; Sex Chromosome Abnormalities/diagnosis* ; X Chromosome* ; Y Chromosome*